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  • 1.
    Aljabery, Firas
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Lindblom, Gunnar
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Skoog, Susann
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.2015In: BMC urology, ISSN 1471-2490, Vol. 15, no 1, p. 87-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We studied patients treated with radical cystectomy for locally advanced bladder cancer to compare the results of both preoperative positron emission tomography/computed tomography (PET/CT) and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes.

    METHODS: Patients who had bladder cancer and were candidates for cystectomy underwent preoperative PET/CT using 18-fluorodeoxyglucose (FDG) and conventional CT. The results regarding lymph node involvement were independently evaluated by two experienced radiologists and were subsequently compared with histopathology results, the latter of which were reassessed by an experienced uropathologist (HO).

    RESULTS: There were 54 evaluable patients (mean age 68 years, 47 [85 %] males and 7 [15 %] females) with pT and pN status as follows: < pT2-14 (26 %), pT2-10 (18 %), and > pT2-30 (56 %); pN0 37 (69 %) and pN+ 17 (31 %). PET/CT showed positive lymph nodes in 12 patients (22 %), and 7 of those cases were confirmed by histopathology; the corresponding results for conventional CT were 11 (20 %) and 7 patients (13 %), respectively. PET/CT had 41 % sensitivity, 86 % specificity, 58 % PPV, and 76 % NPV, whereas the corresponding figures for conventional CT were 41 %, 89 %, 64 %, and 77 %. Additional analyses of the right and left side of the body or in specified anatomical regions gave similar results.

    CONCLUSIONS: In this study, PET/CT and conventional CT had similar low sensitivity in detecting and localizing regional lymph node metastasis in bladder cancer.

  • 2.
    Aljabery, Firas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    M2-macrophage infiltration and macrophage traits of tumor cells in urinary bladder cancer2018In: Urologic Oncology, ISSN 1078-1439, E-ISSN 1873-2496, Vol. 36, no 4, article id 159.e19Article in journal (Refereed)
    Abstract [en]

    Background

    Tumor-associated macrophages (TAMs) constitute a subset of nonneoplastic cells in tumor stroma and influence cancer progression in solid tumors. The clinical significance of TAMs in urinary bladder cancer(UBC) is controversial.

    Methods

    We prospectively studied 103 patients with stage pT1–T4 UBC treated with cystectomy and pelvic lymph node dissection. Tumor sections were immunostained with M2-specific macrophage marker CD163 and proliferation marker Ki-67. The expression of these markers in cancer cells as well as macrophage infiltration (MI) in tumor stroma was analyzed in relation to clinical data and outcome.

    Results

    The mean rate of CD163 and Ki-67 expressed by cancer cells were 35% and 78%, respectively. With borderline significance, MI was associated with lower rate of lymph node metastasis (P = 0.06). CD163 expression in cancer cells was proportional to MI (P<0.014). Patients with CD163-positive tumors and strong MI had significantly longer cancer-specific survival (CSS) (76 months), compared to patient with CD163-positive tumors and weak MI (28 months) (P = 0.02).

    Conclusions

    M2-specific MI tends to be inversely correlated with LN metastasis and improved CSS in UBC. MI might have protective impact in CD163-positive tumors. Expression of CD163 in cancer cells is significantly correlated with MI and might have a tumor promoting impact.

  • 3.
    Aljabery, Firas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Department of Breast and Endocrine Surgery, Karolinska University Hospital, Solna Stockholm, Sweden .
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Jahnson, Staffan
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology.
    Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study.2017In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 120, no 3, p. 329-336Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate the possibility of detecting sentinel lymph nodes (SNs) in patients with urinary bladder cancer (BCa) intra-operatively and whether the histopathological status of the identified SNs reflected that of the lymphatic field.

    PATIENTS AND METHODS: We studied 103 patients with BCa pathological stage T1-T4 who were treated with cystectomy and pelvic lymph node (LN) dissection during 2005-2011 at the Department of Urology, Linköping University Hospital. Radioactive tracer Nanocoll 70 MBq and blue dye were injected into the bladder wall around the primary tumour before surgery. SNs were detected ex vivo during the operation with a handheld Geiger probe (Gamma Detection System; Neoprobe Corp., Dublin, OH, USA). All LNs were formalin-fixed, sectioned three times, mounted on slides and stained with haematoxylin and eosin. An experienced uropathologist evaluated the slides.

    RESULTS: The mean age of the patients was 69 years, and 80 (77%) were male. Pathological staging was T1-12 (12%), T2-20 (19%), T3-48 (47%) and T4-23 (22%). A mean (range) number of 31 (7-68) nodes per patient were examined, totalling 3 253 nodes. LN metastases were found in 41 patients (40%). SNs were detected in 83 of the 103 patients (80%). Sensitivity and specificity for detecting metastatic disease by SN biopsy (SNB) varied between LN stations, with average values of 67% and 90%, respectively. LN metastatic density (LNMD) had a significant prognostic impact; a value of ≥8% was significantly related to shorter survival. Lymphovascular invasion (LVI) occurred in 65% of patients (n = 67) and was significantly associated with shorter cancer-specific survival (P < 0.001).

    CONCLUSION: We conclude that SNB is not a reliable technique for peri-operative localization of LN metastases during cystectomy for BCa; however, LNMD has a significant prognostic value in BCa and may be useful in the clinical context and in BCa oncological and surgical research. LVI was also found to be a prognostic factor.

  • 4.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Behm, Pascal
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology. University of Applied Sciences in Northwest Switzerland.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Fluorescence spectroscopy using indocyanine green for lymph node mapping2014Conference paper (Refereed)
    Abstract [en]

    The principles of cancer treatment has for years been radical resection of the primary tumor. In the oncologic surgeries where the affected cancer site is close to the lymphatic system, it is as important to detect the draining lymph nodes for metastasis (lymph node mapping). As a replacement for conventional radioactive labeling, indocyanine green (ICG) has shown successful results in lymph node mapping; however, most of the ICG fluorescence detection techniques developed are based on camera imaging. In this work, fluorescence spectroscopy using a fiber-optical probe was evaluated on a tissue-like ICG phantom with ICG concentrations of 6-64 μM and on breast tissue from five patients. Fiber-optical based spectroscopy was able to detect ICG fluorescence at low intensities; therefore, it is expected to increase the detection threshold of the conventional imaging systems when used intraoperatively. The probe allows spectral characterization of the fluorescence and navigation in the tissue as opposed to camera imaging which is limited to the view on the surface of the tissue

  • 5.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Medicine and Health Sciences.
    Petersson, Pernilla
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Optical Coherence Tomography for Pathological Analysis of Thyroid2016Conference paper (Refereed)
  • 6.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Stepp, Herbert
    Ludwig Maximilians Universitet, München.
    Markwardt, Niklas
    Ludwig Maximilians Universitet, München.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Optical biopsy during thyroid and parathyroid surgery2015Conference paper (Refereed)
  • 7.
    Lindström, Annelie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Midtbö, Kristine Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Arnesson, Lars-Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Garvin, Stina
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Fusion between M2-macrophages and cancer cells results in a subpopulation of radioresistant cells with enhanced DNA-repair capacity2017In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 31, p. 51370-51386Article in journal (Refereed)
    Abstract [en]

    Cell fusion is a natural biological process in normal development and tissue regeneration. Fusion between cancer cells and macrophages results in hybrids that acquire genetic and phenotypic characteristics from both maternal cells. There is a growing body of in vitro and in vivo data indicating that this process also occurs in solid tumors and may play a significant role in tumor progression. However, investigations of the response of macrophage: cancer cell hybrids to radiotherapy have been lacking. In this study, macrophage: MCF-7 hybrids were generated by spontaneous in vitro cell fusion. After irradiation, both hybrids and their maternal MCF-7 cells were treated with 0 Gy, 2.5 Gy and 5 Gy.-radiation and examined by clonogenic survival and comet assays at three time points (0 h, 24 h, and 48 h). Compared to maternal MCF-7 cells, the hybrids showed increased survival fraction and plating efficiency (colony formation ability) after radiation. The hybrids developed less DNA-damage, expressed significantly lower residual DNA-damage, and after higher radiation dose showed less heterogeneity in DNA-damage compared to their maternal MCF-7 cells. To our knowledge this is the first study that demonstrates that macrophage: cancer cell fusion generates a subpopulation of radioresistant cells with enhanced DNA-repair capacity. These findings provide new insight into how the cell fusion process may contribute to clonal expansion and tumor heterogeneity. Furthermore, our results provide support for cell fusion as a mechanism behind the development of radioresistance and tumor recurrence.

  • 8.
    Nilsson, Isabelle
    et al.
    Linköping University, Department of Medicine and Care. Linköping University, Faculty of Health Sciences.
    Shabo, Ivan
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Svanvik, Joar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Monstein, Hans-Jurg
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Molecular Biological Techniques.
    Multiple displacement amplification of isolated DNA from human gallstones: Molecular identification of Helicobacter DNA by means of 16S rDNA-based pyrosequencing analysis2005In: Helicobacter, ISSN 1083-4389, E-ISSN 1523-5378, Vol. 10, no 6, p. 592-600Article in journal (Refereed)
    Abstract [en]

    Background. Molecular typing of Helicobacter spp. in clinical biopsy specimens has become increasingly important. By means of nested polymerase chain reaction (PCR) amplification and Southern blot analysis of the PCR amplicons, we have shown that Helicobacter spp. DNA is present in human gallstones. In this study we have investigated the possibility of using multiple displacement amplification (MDA) of isolated gallstone DNA and pyrosequencing analysis for the molecular identification of Helicobacter spp. Materials and Methods. DNA isolated from the nucleus of 33 human gallstones and one control strain were used in a MDA assay. Subsequently, pyrosequencing analysis was performed either directly on MDA-DNA using primers flanking the Helicobacter spp. 16S rDNA variable V3 region or on PCR amplicons derived from broad-range primers flanking the 16S rDNA variable V3, V4, and V9 regions. Results. Pyrosequencing analysis of 16S rDNA derived from MDA-DNA revealed that Helicobacter spp.-like DNA was present in 25 of 33 (approximately 76%) gallstones. Using an H. pylori-specific Southern blot analysis, Helicobacter spp.-like DNA was present in 20 of 33 [approximately 61%] of the gallstones. Using MDA-DNA directly in pyrosequencing analysis, Helicobacter spp.-like DNA was present in 13 of 33 [approximately 39%] gallstones. Conclusions. We conclude that multiple displacement amplification combined with pyrosequencing enables a rapid and accurate molecular typing of Helicobacter spp. from small and precious biopsy specimens. © 2005 The Authors Journal compilation © 2005 Blackwell Publishing Ltd.

  • 9.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Macrophage antigen expression in breast and colorectal cancers: A consequence of macrophage - tumour cell fusion?2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Carcinogenesis is a sophisticated biological process consisting of a series of progressive changes in somatic cells from premalignant to malignant phenotype. Despite the vast information available about cancer cells, the origin of cancer and cause of metastasis still remain enigmatic. The hypothesis of cell fusion is one of several models explaining the evolution of neoplasia into clinically significant cancer. This theory states that cancer cells through heterotypic fusion with host cells generate hybrids expressing traits from both parental cells, and acquire metastatic potentials and growth-promoting properties. The cell fusion theory is still unproven and speculative, but cell fusion is a common biological process in normal tissue. Accumulated evidence shows that macrophage-cancer cell fusion occurs in vitro and in vivo and produces hybrids with metastatic potential, but the clinical significant of cell fusion is unclear. The aim of this thesis is to test this hypothesis in clinical patient materials and to explore the clinical significance of macrophage phenotype traits in solid tumours.

    Paraffin-embedded cancer and normal tissue specimens from patients with breast cancer (n=133) and colorectal cancer (two different patient materials with totally 240 patients) were immunostained for the macrophage-specific antigen, CD163. The expression of CD163 was tested in relation to macrophage infiltration and tumour stage, survival time, irradiation, DNA ploidy, cancer cell proliferation and apoptosis.

    Phenotypic macrophage traits, such as the expression of CD163, were seen in both breast and colorectal cancers, and were correlated to advanced tumour stages and poor survival. CD163 expression was more frequent in rectal cancer after irradiation and was associated with decreased apoptosis. Cancer cell proliferation was correlated to both macrophage infiltration and CD163 expression. Multivariate analysis showed that CD163 is a significant prognostic factor in both breast and colorectal cancers.

    In an attempt to examine factors related to the function of macrophage fusion, the expression of the signalling adaptor protein DAP12 was tested and related to CD163 expression in breast cancers from 133 patients. DAP12 was shown to occur in breast cancer cells and was related to high histologic tumour grade, skeletal and liver metastasis, and poor prognosis. The findings in this thesis support the cell fusion theory and illustrate its clinical impact on tumour progression and metastasis.

    List of papers
    1. Breast cancer expression of CD163, a macrophage scavenger receptor, is related to early distant recurrence and reduced patient survival
    Open this publication in new window or tab >>Breast cancer expression of CD163, a macrophage scavenger receptor, is related to early distant recurrence and reduced patient survival
    Show others...
    2008 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 123, no 4, p. 780-786Article in journal (Refereed) Published
    Abstract [en]

    Cells of the monocyte/macrophage lineage are important for tumour cell migration, invasion and metastasis. Fusion between macrophages and cancer cells in animal models in vitro and in vivo causes hybrids with increased metastatic potential. Primary breast cancer cells were characterized for macrophage antigens to test if phenotypic resemblance to macrophages is related to early distant recurrence. Immunostaining for CD163, MAC387 and CD68 was performed in a breast cancer tissue micro array from 127 patients consequently followed up for a median of 13 years. Tumour-associated macrophages expressed all 3 antigens. The breast cancers expressed CD163 to 48%, MAC387 to 14% while CD68 was not expressed. TGF-β staining intensity was positively related to both CD163 and MAC387 expression. Expression of CD163 in the cancer cells was compared to their DNA ploidy, Nottingham Histological Grade, TNM-stage, node state, presence of estrogen receptors and occurrence of distant metastases and survival. Cancers of a more advanced histological grade expressed CD163 to a higher extent. Cells expressing MAC387 were more common in cancers with a high proportion of CD163 positive cells. Multivariate analysis showed that expression of the macrophage antigen CD163 in breast cancer cells has a prognostic impact on the occurrence of distant metastases and reduced patient survival time.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-43420 (URN)10.1002/ijc.23527 (DOI)73820 (Local ID)73820 (Archive number)73820 (OAI)
    Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
    2. Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time.
    Open this publication in new window or tab >>Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time.
    2009 (English)In: International journal of cancer. Journal international du cancer, ISSN 1097-0215, Vol. 125, no 8, p. 1826-1831Article in journal (Refereed) Published
    Abstract [en]

    Expression of the macrophage antigen CD163 in breast cancer cells is recently shown to be related to early distant recurrence and shortened survival. In this study, 163 patients with rectal cancer, included in the Swedish rectal cancer trial and followed up for a median of 71 months, were examined for the expression of CD163 in the primary tumors. The cancer cells expressed CD163 in the primary tumors in 23% (n = 32) of the patients. In pretreatment biopsies from 101 patients, 10 had CD163-positive cancers and these patients had earlier local recurrence (p < 0.044) and reduced survival time (p < 0.045) compared with those with CD163-negative tumors. When studying surgical specimens from 61 patients randomized to preoperative irradiation (5 x 5 Gy delivered in 1 week), it was found that 31% were CD163 positive whereas the corresponding figure was only 17% for 78 patients who were nonirradiated (p < 0.044), which tentatively may be consistent with X-rays inducing fusion. In CD163-positive tumors there was a reduced apoptotic activity as measured with the Termina deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) technique (p = 0.018). There tended also to be an increased proliferation activity measured as an expression of Ki-67 non significant (NS). It is concluded that primary rectal cancers may express CD-163, and this phenotypic macrophage trait is related to early local recurrence, shorter survival time and reduced apoptosis. Furthermore, the expression of CD163 is more common after irradiation.

    Keywords
    rectal cancer • macrophages • metastasis • survival • cell fusion • radiotherapy
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-21408 (URN)10.1002/ijc.24506 (DOI)19582880 (PubMedID)
    Available from: 2009-10-01 Created: 2009-10-01 Last updated: 2010-04-14
    3. Tumor cell expression of CD163 is an independent prognostic factor in colorectal cancer patients
    Open this publication in new window or tab >>Tumor cell expression of CD163 is an independent prognostic factor in colorectal cancer patients
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    CD163 is a macrophage specific marker. Recent studies have shown that CD163 expression in breast and rectal cancer cells is associated with poor prognosis. This study was conducted to evaluate the relationship between CD163 expression, as a macrophage trait, and macrophage infiltration and their clinical-pathological significance in colorectal cancer. The hypothesis of macrophage-cancer cell fusion may explain the expression of CD163 in cancer cells.

    Immune-staining of CD163 and macrophage infiltration were evaluated in paraffinembedded specimens, earlier analyzed for Ki-67, CD31 and D2-40 and S-phase fraction, from primary tumors and normal colorectal mucosa of 77 patients with colorectal carcinoma. The outcomes were analyzed in relation to clinical-pathological data.

    CD163 is positive in cancer cells in 16-18% of the patients and it is related to advanced tumor stages (stage III-IV) and unfavorable prognosis. High macrophage infiltration may be related to lower survival but this relation was not statistically significant. The prognostic significance of CD163 expression is independent of tumor stage (p=0,015) and macrophage density in tumor stroma (p=0,007).

    The expression of macrophage phenotype in colorectal cancer cells is associated with poor prognosis independently of tumor stage and macrophage density in the tumour stroma. Macrophages may promote tumour growth and progression by an autocrine interaction with cancer cells. Macrophage – cancer cell fusion may occur in colorectal cancer and contribute to tumour progression and metastasis.

    Keywords
    Colorectal cancer, tumour associated macrophages, macrophage infiltration, CD163, cell fusion
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-54818 (URN)
    Available from: 2010-04-14 Created: 2010-04-14 Last updated: 2010-04-14Bibliographically approved
    4. DAP12, a macrophage fusion receptor, is expressed in breast cancer cells and associated with skeletal and liver metastases and poor survival
    Open this publication in new window or tab >>DAP12, a macrophage fusion receptor, is expressed in breast cancer cells and associated with skeletal and liver metastases and poor survival
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    DAP12 is a transmembrane receptor present in myeloid cells and is essential for the development of functionally mature osteoclasts and microglia, and for integrin signaling in macrophages and neutrophils. The macrophage specific antigen CD163 is expressed in breast and colorectal cancer and is associated with early cancer recurrence and poor prognosis. We hypothesize that macrophage traits in cancer cells may be explained by fusion between cancer cells and tumor associated macrophages. The role of DAP12 in the fusion between cancer cells and macrophages is not known. This study was performed to investigate the expression of DAP12 in breast cancer cells and its´ relation to macrophage trait manifested by CD163 expression.

    Immunostaining of DAP12, CD163 and MAC387 were evaluated in paraffinembedded specimens from totally 133 patients with breast cancer. The outcomes were analyzed in relation to clinicopathological data.

    DAP12 expression was positive in the majority of cases (64%) with breast cancer and associated with advanced tumor grade (p= 0.015) and liver metastasis (p= 0.0465) but not lung metastasis (0.997). It tended to correlate with skeletal metastases (p=0.0673). Patients with breast cancer expressing high DAP12 had poor prognosis with higher rates of skeletal (p=0.023) and liver metastases (p=0.028) and overall shorter distant recurrence free survival (p=0.0028). DAP12 expression was neither correlated to CD163 nor MAC387 expression. To our knowledge, this is the first study where DAP12 expression is reported in breast cancer.

    In conclusion, DAP12 is expressed in breast cancer and is significantly related to skeletal and liver metastasis as well as poor prognosis. We hypothesize that DAP12 expression may promote fusion between breast cancer cells and macrophages. It may even promote homing of cancer cells in bone and liver tissue and result in increased metastasis at these sites.

    Keywords
    Breast cancer, tumour associated macrophages, DAP12, CD163, metastasis, cell fusion
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-54819 (URN)
    Available from: 2010-04-14 Created: 2010-04-14 Last updated: 2010-04-14
  • 10.
    Shabo, Ivan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Midtbö, Kristine Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Andersson, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Åkerlund, Emma
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Wegman, Pia
    Linköping University, Department of Clinical and Experimental Medicine. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics. Linköping University, Faculty of Medicine and Health Sciences.
    Gunnarsson, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics. Linköping University, Faculty of Medicine and Health Sciences.
    Lindström, Annelie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Macrophage traits in cancer cells are induced by macrophage-cancer cell fusion and cannot be explained by cellular interaction2015In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 15, no 1, p. 922-Article in journal (Refereed)
    Abstract [en]

    Background: Cell fusion is a natural process in normal development and tissue regeneration. Fusion between cancer cells and macrophages generates metastatic hybrids with genetic and phenotypic characteristics from both maternal cells. However, there are no clinical markers for detecting cell fusion in clinical context. Macrophage-specific antigen CD163 expression in tumor cells is reported in breast and colorectal cancers and proposed being caused by macrophages-cancer cell fusion in tumor stroma. The purpose of this study is to examine the cell fusion process as a biological explanation for macrophage phenotype in breast. Methods: Monocytes, harvested from male blood donor, were activated to M2 macrophages and co-cultured in ThinCert transwell system with GFP-labeled MCF-7 cancer cells. MCF7/macrophage hybrids were generated by spontaneous cell fusion, isolated by fluorescence-activated cell sorting and confirmed by fluorescence microscopy, short tandem repeats analysis and flow cytometry. CD163 expression was evaluated in breast tumor samples material from 127 women by immunohistochemistry. Results: MCF-7/macrophage hybrids were generated spontaneously at average rate of 2 % and showed phenotypic and genetic traits from both maternal cells. CD163 expression in MCF-7 cells could not be induced by paracrine interaction with M2-activated macrophages. CD163 positive cancer cells in tumor sections grew in clonal collection and a cutoff point greater than25 % of positive cancer cells was significantly correlated to disease free and overall survival. Conclusions: In conclusion, macrophage traits in breast cancer might be caused by cell fusion rather than explained by paracrine cellular interaction. These data provide new insights into the role of cell fusion in breast cancer and contributes to the development of clinical markers to identify cell fusion.

  • 11.
    Shabo, Ivan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Tumor cell expression of CD163 is an independent prognostic factor in colorectal cancer patientsManuscript (preprint) (Other academic)
    Abstract [en]

    CD163 is a macrophage specific marker. Recent studies have shown that CD163 expression in breast and rectal cancer cells is associated with poor prognosis. This study was conducted to evaluate the relationship between CD163 expression, as a macrophage trait, and macrophage infiltration and their clinical-pathological significance in colorectal cancer. The hypothesis of macrophage-cancer cell fusion may explain the expression of CD163 in cancer cells.

    Immune-staining of CD163 and macrophage infiltration were evaluated in paraffinembedded specimens, earlier analyzed for Ki-67, CD31 and D2-40 and S-phase fraction, from primary tumors and normal colorectal mucosa of 77 patients with colorectal carcinoma. The outcomes were analyzed in relation to clinical-pathological data.

    CD163 is positive in cancer cells in 16-18% of the patients and it is related to advanced tumor stages (stage III-IV) and unfavorable prognosis. High macrophage infiltration may be related to lower survival but this relation was not statistically significant. The prognostic significance of CD163 expression is independent of tumor stage (p=0,015) and macrophage density in tumor stroma (p=0,007).

    The expression of macrophage phenotype in colorectal cancer cells is associated with poor prognosis independently of tumor stage and macrophage density in the tumour stroma. Macrophages may promote tumour growth and progression by an autocrine interaction with cancer cells. Macrophage – cancer cell fusion may occur in colorectal cancer and contribute to tumour progression and metastasis.

  • 12.
    Shabo, Ivan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Elkarim, Rihab
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Svanvik, Joar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Macrophage Infiltration in Tumor Stroma is Related to Tumor Cell Expression of CD163 in Colorectal Cancer2014In: Cancer Microenvironment, ISSN 1875-2292, E-ISSN 1875-2284, Vol. 7, no 1, p. 61-69Article in journal (Refereed)
    Abstract [en]

    The scavenger receptor, CD163, is a macrophage-specific marker. Recent studies have shown that CD163 expression in breast and rectal cancer cells is associated with poor prognosis. This study was conducted to evaluate the relationship between CD163 expression as a macrophage trait in cancer cells, and macrophage infiltration and its clinical significance in colorectal cancer. Immunostaining of CD163 and macrophage infiltration were evaluated in paraffin-embedded specimens, earlier analyzed for CD31, D2-40 and S-phase fraction, from primary tumors and normal colorectal mucosa of 75 patients with colorectal carcinoma. The outcomes were analyzed in relation to clinical-pathological data. CD163 expression was positive in cancer cells in 20 % of colorectal cancer patients and was related to advanced tumor stages (P = 0.008) and unfavorable prognosis (p = 0.001). High macrophage infiltration was related to shorter survival and positive CD163 expression in tumor cells. The prognostic impact of macrophage infiltration was independent of tumor stage and CD163 expression in cancer cells (p = 0.034). The expression of macrophage phenotype in colorectal cancer cells is associated with macrophage density in tumor stroma and lower survival rates. Macrophage infiltration has an independent prognostic impact on mortality in colorectal cancer. In accordance with previous experimental studies, these findings provide new insights into the role of macrophages in colorectal cancer.

  • 13.
    Shabo, Ivan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Svanvik, Joar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Breast Cancer Expression of DAP12 is Associated With Skeletal and Liver Metastases and Poor Survival2013In: Clinical Breast Cancer, ISSN 1526-8209, E-ISSN 1938-0666, Vol. 13, no 5, p. 371-377Article in journal (Refereed)
    Abstract [en]

    Macrophages are an important cellular factor in breast cancer (BRC) progression and metastasis. DNAX activating protein of 12 kD (DAP12) is essential factor for macrophage fusion function. This study was conducted to investigate the expression and significance of DAP12 expression in BRC. DAP12 is expressed in BRC cells and associated with poor survival, liver metastases, and bone metastases. These data provide new insight into the pathophysiology of macrophages in BRC. less thanbrgreater than less thanbrgreater thanBackground: The transmembrane adapter protein, DAP12, transduces activation signals for several arrays of receptors, including human signal-regulatory protein, DAP12-associating lectin-1, triggering receptor expressed on myeloid cells-1, -2, and -3, in natural killer cells, granulocytes, monocytes/macrophages, and dendritic cells. The macrophage-specific antigen, Cluster of Differentiation 163 (CD163), is expressed in breast and colorectal cancers and is associated with early cancer recurrence and poor prognosis. It was recently shown that fusion between intestinal tumor cells and macrophages results in nuclear reprogramming with hybrid transcripts from both cells of origin. The role of DAP12 in the fusion process is not known. This study investigates the expression of DAP12 in BRC cells, and its relation to other macrophage traits and to the clinical progression of disease. Materials and Methods: Immunostaining of DAP12 and CD163 was performed and evaluated in paraffin-embedded specimens from 132 patients with BRC. The outcomes were analyzed in relation to clinicopathological data. Results: DAP12 expression in cancer cells was positive in 66 percent of the cancers and was associated with high tumor grade (P = .015), and with liver (P = .047) and skeletal (P = .067), but not with lung metastases (P = 1.00). Patients with BRC expressing DAP12 had poor prognosis, with higher recurrence rates of skeletal (P = .018) and liver metastases (P = .047), and shorter survival time (P = .0060). Conclusion: We suggest that macrophage traits in BRC cells facilitate the metastatic process and that DAP12 expression might promote metastatic homing to bone and liver tissues.

  • 14.
    Shabo, Ivan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Svanvik, Joar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    DAP12, a macrophage fusion receptor, is expressed in breast cancer cells and associated with skeletal and liver metastases and poor survivalManuscript (preprint) (Other academic)
    Abstract [en]

    DAP12 is a transmembrane receptor present in myeloid cells and is essential for the development of functionally mature osteoclasts and microglia, and for integrin signaling in macrophages and neutrophils. The macrophage specific antigen CD163 is expressed in breast and colorectal cancer and is associated with early cancer recurrence and poor prognosis. We hypothesize that macrophage traits in cancer cells may be explained by fusion between cancer cells and tumor associated macrophages. The role of DAP12 in the fusion between cancer cells and macrophages is not known. This study was performed to investigate the expression of DAP12 in breast cancer cells and its´ relation to macrophage trait manifested by CD163 expression.

    Immunostaining of DAP12, CD163 and MAC387 were evaluated in paraffinembedded specimens from totally 133 patients with breast cancer. The outcomes were analyzed in relation to clinicopathological data.

    DAP12 expression was positive in the majority of cases (64%) with breast cancer and associated with advanced tumor grade (p= 0.015) and liver metastasis (p= 0.0465) but not lung metastasis (0.997). It tended to correlate with skeletal metastases (p=0.0673). Patients with breast cancer expressing high DAP12 had poor prognosis with higher rates of skeletal (p=0.023) and liver metastases (p=0.028) and overall shorter distant recurrence free survival (p=0.0028). DAP12 expression was neither correlated to CD163 nor MAC387 expression. To our knowledge, this is the first study where DAP12 expression is reported in breast cancer.

    In conclusion, DAP12 is expressed in breast cancer and is significantly related to skeletal and liver metastasis as well as poor prognosis. We hypothesize that DAP12 expression may promote fusion between breast cancer cells and macrophages. It may even promote homing of cancer cells in bone and liver tissue and result in increased metastasis at these sites.

  • 15.
    Shabo, Ivan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Svanvik, Joar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time.2009In: International journal of cancer. Journal international du cancer, ISSN 1097-0215, Vol. 125, no 8, p. 1826-1831Article in journal (Refereed)
    Abstract [en]

    Expression of the macrophage antigen CD163 in breast cancer cells is recently shown to be related to early distant recurrence and shortened survival. In this study, 163 patients with rectal cancer, included in the Swedish rectal cancer trial and followed up for a median of 71 months, were examined for the expression of CD163 in the primary tumors. The cancer cells expressed CD163 in the primary tumors in 23% (n = 32) of the patients. In pretreatment biopsies from 101 patients, 10 had CD163-positive cancers and these patients had earlier local recurrence (p < 0.044) and reduced survival time (p < 0.045) compared with those with CD163-negative tumors. When studying surgical specimens from 61 patients randomized to preoperative irradiation (5 x 5 Gy delivered in 1 week), it was found that 31% were CD163 positive whereas the corresponding figure was only 17% for 78 patients who were nonirradiated (p < 0.044), which tentatively may be consistent with X-rays inducing fusion. In CD163-positive tumors there was a reduced apoptotic activity as measured with the Termina deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) technique (p = 0.018). There tended also to be an increased proliferation activity measured as an expression of Ki-67 non significant (NS). It is concluded that primary rectal cancers may express CD-163, and this phenotypic macrophage trait is related to early local recurrence, shorter survival time and reduced apoptosis. Furthermore, the expression of CD163 is more common after irradiation.

  • 16.
    Shabo, Ivan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Olsson, Hans
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Doré, Siv
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Svanvik, Joar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Breast cancer expression of CD163, a macrophage scavenger receptor, is related to early distant recurrence and reduced patient survival2008In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 123, no 4, p. 780-786Article in journal (Refereed)
    Abstract [en]

    Cells of the monocyte/macrophage lineage are important for tumour cell migration, invasion and metastasis. Fusion between macrophages and cancer cells in animal models in vitro and in vivo causes hybrids with increased metastatic potential. Primary breast cancer cells were characterized for macrophage antigens to test if phenotypic resemblance to macrophages is related to early distant recurrence. Immunostaining for CD163, MAC387 and CD68 was performed in a breast cancer tissue micro array from 127 patients consequently followed up for a median of 13 years. Tumour-associated macrophages expressed all 3 antigens. The breast cancers expressed CD163 to 48%, MAC387 to 14% while CD68 was not expressed. TGF-β staining intensity was positively related to both CD163 and MAC387 expression. Expression of CD163 in the cancer cells was compared to their DNA ploidy, Nottingham Histological Grade, TNM-stage, node state, presence of estrogen receptors and occurrence of distant metastases and survival. Cancers of a more advanced histological grade expressed CD163 to a higher extent. Cells expressing MAC387 were more common in cancers with a high proportion of CD163 positive cells. Multivariate analysis showed that expression of the macrophage antigen CD163 in breast cancer cells has a prognostic impact on the occurrence of distant metastases and reduced patient survival time.

  • 17.
    Shabo, Ivan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Svanvik, Joar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Expression of Macrophage Antigens by Tumor Cells2011In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 714, p. 141-150Article in journal (Refereed)
    Abstract [en]

    Macrophages are a heterogeneous cell population of the myeloid linage derived from monocytes. These cells show two different polarization states, M1 and M2 macrophages in response to different micro environmental signals. Tumor associated macrophages (TAM) represent the M2 type and promote tumor progression. These cells express antigens that more or less are specific for macrophages like: CD14, CD68, MAC387, CD 163, and DAP12. In a series of recent studies it is shown that cancer cells may express these antigens and CD I 63, MAC387 and DAP12 may be expressed by e.g. breast cancer cells. Thus, 48% of the breast cancers expressed CD163 that is a scavenger receptor normally expressed by macrophages alone. The corresponding figure for rectal cancer is 31%. The expression of CD163 is correlated to early distant recurrence in breast cancer and local recurrence in rectal cancer and reduced survival time in both conditions. Expression of macrophage antigens in breast- and colorectal-cancers may have a prognostic relevance in clinical praxis. One explanation to these findings is that resemblance with macrophages may indicate a more invasive phenotype due to genetic exchange between the primary tumor cells and associated macrophages. This is further supported by the finding that expression of DAP12, a macrophage fusion receptor, in breast cancer is associated with an advanced tumor grade and higher rates of skeletal and liver metastases and overall shorter distant recurrence free survival. Another explanation to the changed phenotype is a genetic exchange between the cells by exosome-mediated transfer.

  • 18.
    Svanvik, Joar
    et al.
    Sahlgrenska Hospital, Gothenburg, Sweden.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Review and rhyme: of birth of cancers and selfish epigenomes2014In: Medical Hypotheses, ISSN 0306-9877, E-ISSN 1532-2777, Vol. 82, no 5, p. 639-640Article in journal (Other academic)
    Abstract [en]

    n/a

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