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Olsson, Hans
Publications (10 of 35) Show all publications
Falck, A. K., Rome, A., Ferno, M., Olsson, H., Chebil, G., Bendahl, P. O. & Ryden, L. (2016). St Gallen molecular subtypes in screening-detected and symptomatic breast cancer in a prospective cohort with long-term follow-up. British Journal of Surgery, 103(5), 513-523
Open this publication in new window or tab >>St Gallen molecular subtypes in screening-detected and symptomatic breast cancer in a prospective cohort with long-term follow-up
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2016 (English)In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 103, no 5, p. 513-523Article in journal (Refereed) Published
Abstract [en]

Background: Diagnosis by screening mammography is considered an independent positive prognostic factor, although the data are not fully in agreement. The aim of the study was to explore whether the mode of detection (screening-detected versus symptomatic) adds prognostic information to the St Gallen molecular subtypes of primary breast cancer, in terms of 10-year cumulative breast cancer mortality (BCM). Methods: A prospective cohort of patients with primary breast cancer, who had regularly been invited to screening mammography, were included. Tissue microarrays were constructed from primary tumours and lymph node metastases, and evaluated by two independent pathologists. Primary tumours and lymph node metastases were classified into St Gallen molecular subtypes. Cause of death was retrieved from the Central Statistics Office. Results: A total of 434 patients with primary breast cancer were included in the study. Some 370primary tumours and 111 lymph node metastases were classified into St Gallen molecular subtypes. The luminal A-like subtype was more common among the screening-detected primary tumours (P=0.035) and corresponding lymph node metastases (P=0.114) than among symptomatic cancers. Patients with screening-detected tumours had a lower BCM (P=0.017), and for those diagnosed with luminal A-like tumours the 10-year cumulative BCM was 3 per cent. For patients with luminal A-like lymph node metastases, there was no BCM. In a stepwise multivariable analysis, the prognostic information yielded by screening detection was hampered by stage and tumour biology. Conclusion: The prognosis was excellent for patients within the screening programme who were diagnosed with a luminal A-like primary tumour and/or lymph node metastases. Stage, molecular pathology and mode of detection help to define patients at low risk of death from breast cancer.

Place, publisher, year, edition, pages
WILEY-BLACKWELL, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-127415 (URN)10.1002/bjs.10070 (DOI)000372914100006 ()26856820 (PubMedID)
Note

Funding Agencies|Swedish Breast Cancer Organization (BRO); Swedish Cancer Society [2010/1234, 2010/501]; Gunnar Nilsson Cancer Foundation [2013/1224]; Mrs Berta Kamprad Foundation [2014/36]; Skane County Councils Research and Development Foundation [2014/45208]; Governmental Funding of Clinical Research within National Health Service (ALF) [2014/434901]; Gyllenstiernska Krapperup Foundation [2014/1702]; Stig and Ragna Gorthons Stiftelse

Available from: 2016-05-02 Created: 2016-04-26 Last updated: 2017-11-30
Ekholm, M., Grabau, D., Bendahl, P.-O., Bergh, J., Elmberger, G., Olsson, H., . . . Ferno, M. (2015). Highly reproducible results of breast cancer biomarkers when analysed in accordance with national guidelines - a Swedish survey with central re-assessment. Acta Oncologica, 54(7), 1040-1048
Open this publication in new window or tab >>Highly reproducible results of breast cancer biomarkers when analysed in accordance with national guidelines - a Swedish survey with central re-assessment
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2015 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, no 7, p. 1040-1048Article in journal (Refereed) Published
Abstract [en]

Background. Biomarkers are crucial for decisions regarding adjuvant therapy in primary breast cancer, and their correct assessment is therefore of the utmost importance. Aims. To investigate the concordance between Swedish pathology departments and a reference laboratory, for routine analysis of oestrogen receptor (ER), progesterone receptor (PR), Ki67, and human epidermal growth factor receptor 2 (HER2), alone, and in combination (St Gallen subtypes). Methods. This survey included 27 of the 28 pathology laboratories in Sweden, covering 98% of cases of primary breast cancer surgery in Sweden. Paraffin-embedded tumour blocks (n = 270) were collected and sent to the central reference laboratory, together with the originally stained slides, for re-analysis. The primary evaluations were previously performed according to national Swedish guidelines, without any knowledge of the subsequent central assessment. Results. The agreement for ER, PR, and Ki67 was 99% [kappa value (kappa) = 0.95], 95% (kappa = 0.85), and 85% (kappa = 0.70), respectively. The agreement for HER2 (0/1 + vs. 2+/3+) was 85% (kappa = 0.64), but when equivocal tumours were further analysed with in situ hybridisation, only one discrepancy was observed. Discrepancies between results for ER and PR seem to be explained by analytical differences, whereas the interpretation of staining seems to be more critical for Ki67 and HER2 immunohistochemistry. The agreement between the results from the Swedish laboratories and the reference laboratory, based on the St Gallen subtypes, was 88% (kappa = 0.81). Conclusions. When applying national guidelines, highly reproducible results were obtained in routine assessment of breast cancer biomarkers, and the results of this study confirm the clinical utility of these markers for decisions regarding the treatment of primary breast cancer.

Place, publisher, year, edition, pages
TAYLOR and FRANCIS LTD, 2015
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-121917 (URN)10.3109/0284186X.2015.1037012 (DOI)000361284900011 ()25959664 (PubMedID)
Note

Funding Agencies|Swedish Breast Cancer Association (BRO); Futurum - the Academy of Health and Care; Jonkoping County Council; Foundation for Clinical Cancer Research in Jonkoping

Available from: 2015-10-13 Created: 2015-10-12 Last updated: 2017-12-01
Shabo, I., Midtbö, K. M., Andersson, H., Åkerlund, E., Olsson, H., Wegman, P., . . . Lindström, A. (2015). Macrophage traits in cancer cells are induced by macrophage-cancer cell fusion and cannot be explained by cellular interaction. BMC Cancer, 15(1), 922
Open this publication in new window or tab >>Macrophage traits in cancer cells are induced by macrophage-cancer cell fusion and cannot be explained by cellular interaction
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2015 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 15, no 1, p. 922-Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2015
Keywords
Cell fusion; Macrophages; Paracrine cellular interaction; Tumor markers
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-123328 (URN)10.1186/s12885-015-1935-0 (DOI)000365276000001 ()26585897 (PubMedID)
Note

Funding Agencies|County Council of Ostergotland (Sweden); National Organization of Breast Cancer Associations (Sweden); Bengt Ihre Foundation (Swedish Surgical Society)

Available from: 2015-12-14 Created: 2015-12-11 Last updated: 2018-01-10
Bojmar, L., Zhang, H., Costa da Silva, B., Karlsson, E., Olsson, H., Vincent, T., . . . Sandström, P. (2015). miR-18a is regulated between progressive compartments of cancers, and incorporated in exosomes with the potential of creating premetastatic niches and predict cancer outcome.
Open this publication in new window or tab >>miR-18a is regulated between progressive compartments of cancers, and incorporated in exosomes with the potential of creating premetastatic niches and predict cancer outcome
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2015 (English)Manuscript (preprint) (Other academic)
Abstract [en]

The ultimate cause of death for many cancer patients is the spread of the cancer via metastasis. Even so, there are still a lack of knowledge regarding the metastasis process. This study was performed to investigate the role of metastamirs in exosomes and their metastatic patterns. We used the well-established isogeneic murine cancer model of low metastatic 67NR cells, mimicking luminal/basal breast tumors, and highly metastatic 4T1 cells with characteristics of basal breast  tumors. We studied the exosomal properties and pre-metastatic effects in this metastasis model and compared human materials and exosomes of several other tumor types. Our data clearly demonstrated that exosomes from the highly metastatic cells home to the metastatic organs of their parental cells whereas exosomes from cells with low metastatic potential mostly located to lymph nodes. The exosome protein cargos also resembled their parental cells and potentially affects their target organs, and cells, differently. Furthermore, the exosomes from the highly metastatic cells had a more pronounced effect on tumor growth and pre-metastatic changes than the low metastatic exosomes. The microRNA-18a, a predictor of metastasis, was present to a higher extent in metastatic exosomes as compared to low metastatic exosomes, and altered the tumor progressive properties. Our findings support the role of exomirs as important players in the metastatic process, the value as biomarkers and potential therapeutic targets.

National Category
Cancer and Oncology Cell and Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:liu:diva-122829 (URN)
Available from: 2015-11-26 Created: 2015-11-26 Last updated: 2018-01-10Bibliographically approved
Björnsson, B., Bojmar, L., Olsson, H., Sundqvist, T. & Sandström, P. (2015). Nitrite, a novel method to decrease ischemia/reperfusion injury in the rat liver. World Journal of Gastroenterology, 21(6), 1775-1783
Open this publication in new window or tab >>Nitrite, a novel method to decrease ischemia/reperfusion injury in the rat liver
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2015 (English)In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 6, p. 1775-1783Article in journal (Refereed) Published
Abstract [en]

AIM: To investigate whether nitrite administered prior to ischemia/reperfusion (I/R) reduces liver injury.

METHODS: Thirty-six male Sprague-Dawley rats were randomized to 3 groups, including sham operated (n = 8), 45-min segmental ischemia of the left liver lobe (IR, n = 14) and ischemia/reperfusion (I/R) preceded by the administration of 480 nmol of nitrite (n = 14). Serum transaminases were measured after 4 h of reperfusion. Liver microdialysate (MD) was sampled in 30-min intervals and analyzed for glucose, lactate, pyruvate and glycerol as well as the total nitrite and nitrate (NOx). The NOx was measured in serum.

RESULTS: Aspartate aminotransferase (AST) at the end of reperfusion was higher in the IR group than in the nitrite group (40 ± 6.8 μkat/L vs 22 ± 2.6 μkat/L, P = 0.022). Similarly, alanine aminotransferase (ALT) was also higher in the I/R group than in the nitrite group (34 ± 6 μkat vs 14 ± 1.5 μkat, P = 0.0045). The NOx in MD was significantly higher in the nitrite group than in the I/R group (10.1 ± 2.9 μM vs 3.2 ± 0.9 μM, P = 0.031) after the administration of nitrite. During ischemia, the levels decreased in both groups and then increased again during reperfusion. At the end of reperfusion, there was a tendency towards a higher NOx in the I/R group than in the nitrite group (11.6 ± 0.7 μM vs 9.2 ± 1.1 μM, P = 0.067). Lactate in MD was significantly higher in the IR group than in the nitrite group (3.37 ± 0.18 mM vs 2.8 ± 0.12 mM, P = 0.01) during ischemia and the first 30 min of reperfusion. During the same period, glycerol was also higher in the IRI group than in the nitrite group (464 ± 38 μM vs 367 ± 31 μM, P = 0.049). With respect to histology, there were more signs of tissue damage in the I/R group than in the nitrite group, and 29% of the animals in the I/R group exhibited necrosis compared with none in the nitrite group. Inducible nitric oxide synthase (iNOS) transcription increased between early ischemia (t = 15) and the end of reperfusion in both groups.

CONCLUSION: Nitrite administered before liver ischemia in the rat liver reduces anaerobic metabolism and cell necrosis, which could be important in the clinical setting.

Place, publisher, year, edition, pages
Baishideng Publishing Group Co. Limited, 2015
Keywords
Ischemia-reperfusion injury; Nitrite; Liver ischemia; Liver surgery; Microdialysis; Nitric oxide; Inducible nitric oxide synthase
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-110262 (URN)10.3748/wjg.v21.i6.1775 (DOI)000349666300010 ()25684942 (PubMedID)
Available from: 2014-09-05 Created: 2014-09-05 Last updated: 2017-12-05Bibliographically approved
Aljabery, F., Lindblom, G., Skoog, S., Shabo, I., Olsson, H., Rosell, J. & Jahnson, S. (2015). PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.. BMC urology, 15(1), 87
Open this publication in new window or tab >>PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.
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2015 (English)In: BMC urology, ISSN 1471-2490, Vol. 15, no 1, p. 87-Article in journal (Refereed) Published
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.

National Category
Urology and Nephrology Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-120796 (URN)10.1186/s12894-015-0080-z (DOI)000359832000001 ()26294219 (PubMedID)
Available from: 2015-08-25 Created: 2015-08-25 Last updated: 2017-05-17
Aaltonen, K. E., Rosendahl, A. H., Olsson, H., Malmstrom, P., Hartman, L. & Ferno, M. (2014). Association between insulin-like growth factor-1 receptor (IGF1R) negativity and poor prognosis in a cohort of women with primary breast cancer. BMC Cancer, 14(794)
Open this publication in new window or tab >>Association between insulin-like growth factor-1 receptor (IGF1R) negativity and poor prognosis in a cohort of women with primary breast cancer
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2014 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 14, no 794Article in journal (Refereed) Published
Abstract [en]

Background: Resistance towards endocrine therapy is a great concern in breast cancer treatment and may partly be explained by the activation of compensatory signaling pathways. The aim of the present study was to investigate if the insulin-like growth factor-1 receptor (IGF1R) signaling pathway was activated or deregulated in breast cancer patients and to explore if any of the markers were prognostic, with or without adjuvant tamoxifen. This signaling pathway has been suggested to cause estrogen independent cell growth and thus contribute to resistance to endocrine treatment in estrogen receptor (ER) positive breast cancer. Methods: The protein expression of IGF1R, phosphorylated Mammalian Target of Rapamycin (p-mTOR) and phosphorylated S6 ribosomal protein (p-S6rp) were investigated by immunohistochemistry using tissue microarrays in two patient cohorts. Cohort I (N = 264) consisted of mainly postmenopausal women with stage II breast cancer treated with tamoxifen for 2 years irrespective of ER status. Cohort II (N = 206) consisted of mainly medically untreated, premenopausal patients with node-negative breast cancer. Distant disease-free survival (DDFS) at 5 years was used as end-point for survival analyses. Results: We found that lower IGF1R expression was associated with worse prognosis for tamoxifen treated, postmenopausal women (HR = 0.70, 95% CI = 0.52 - 0.94, p = 0.016). The effect was seen mainly in ER-negative patients where the prognostic effect was retained after adjustment for other prognostic markers (adjusted HR = 0.49, 95% CI = 0.29 - 0.82, p = 0.007). Expression of IGF1R was associated with ER positivity (p less than 0.001) in the same patient cohort. Conclusions: Our results support previous studies indicating that IGF1R positivity reflects a well differentiated tumor with low metastatic capacity. An association between lack of IGF1R expression and worse prognosis was mainly seen in the ER-negative part of Cohort I. The lack of co-activation of downstream markers (p-mTOR and p-S6rp) in the IGF1R pathway suggested that the prognostic effect was not due to complete activation of this pathway. Thus, no evidence could be found for a compensatory function of IGF1R signaling in the investigated cohorts.

Place, publisher, year, edition, pages
BioMed Central, 2014
Keywords
Primary breast cancer; Insulin-like growth factor-1 receptor; Estrogen receptor; Tamoxifen; Prognosis
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-112813 (URN)10.1186/1471-2407-14-794 (DOI)000345113300001 ()25362932 (PubMedID)
Note

Funding Agencies|Swedish Cancer Society; Swedish Research Council; Gunnar Nilsson Cancer Foundation; Mrs. Berta Kamprad Foundation; Anna and Edwin Bergers foundation; Skane University Hospital Research Foundation; Skane County Councils Research and Development Foundation; Governmental Funding of Clinical Research within the National Health Service

Available from: 2015-01-08 Created: 2014-12-17 Last updated: 2017-12-05
Shabo, I., Olsson, H., Elkarim, R., Sun, X.-F. & Svanvik, J. (2014). Macrophage Infiltration in Tumor Stroma is Related to Tumor Cell Expression of CD163 in Colorectal Cancer. Cancer Microenvironment, 7(1), 61-69
Open this publication in new window or tab >>Macrophage Infiltration in Tumor Stroma is Related to Tumor Cell Expression of CD163 in Colorectal Cancer
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2014 (English)In: Cancer Microenvironment, ISSN 1875-2292, E-ISSN 1875-2284, Vol. 7, no 1, p. 61-69Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Springer Netherlands, 2014
Keywords
CD163 expression, Macrophage infiltration, Colorectal cancer
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-106894 (URN)10.1007/s12307-014-0145-7 (DOI)24771466 (PubMedID)
Available from: 2014-05-23 Created: 2014-05-23 Last updated: 2017-12-05Bibliographically approved
Falck, A.-K., Bendahl, P.-O., Chebil, G., Olsson, H., Ferno, M. & Ryden, L. (2013). Biomarker expression and St Gallen molecular subtype classification in primary tumours, synchronous lymph node metastases and asynchronous relapses in primary breast cancer patients with 10 years follow-up. Breast Cancer Research and Treatment, 140(1), 93-104
Open this publication in new window or tab >>Biomarker expression and St Gallen molecular subtype classification in primary tumours, synchronous lymph node metastases and asynchronous relapses in primary breast cancer patients with 10 years follow-up
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2013 (English)In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 140, no 1, p. 93-104Article in journal (Refereed) Published
Abstract [en]

Molecular profiles of asynchronous breast cancer metastases are of clinical relevance to individual patients treatment, whereas the role of profiles in synchronous lymph node metastases is not defined. The present study aimed to assess individual biomarkers and molecular subtypes according to the St Gallen classification in primary breast tumours, synchronous lymph node metastases and asynchronous relapses and relate the results to 10-year breast cancer mortality (BCM). Tissue microarrays were constructed from archived tissue blocks of primary tumours (N = 524), synchronous lymph node metastases (N = 147) and asynchronous relapses (N = 36). The samples were evaluated by two independent pathologists according to oestrogen receptor (ER), progesterone receptor (PR), Ki67 and human epidermal growth factor receptor 2 (HER2) by immunohistochemistry and in situ hybridisation. The expression of biomarkers and molecular subtypes in the primary tumour was compared with that in the synchronous lymph node metastases and relapses, and related to 10-year BCM. Discordances were found between primary tumours and relapses (ER: p = 0.006, PR: p = 0.04, Ki67: p = 0.02, HER2: p = 0.02, St Gallen subtypes: p = 0.07) but not between primary tumours and metastatic lymph node. Prognostic information was gained by the molecular subtype classification in primary tumours and nodal metastases; triple negative subtype had the highest BCM compared with the luminal A subtype (primary tumours: HR 4.0; 95 % CI 2.0-8.2, p andlt; 0.001, lymph node metastases: HR 3.5; 95 % CI 1.3-9.7, p = 0.02). When a shift in subtype inherence between primary tumour and metastatic lymph node was identified, the prognosis seemed to follow the subtype of the lymph node. Molecular profiles are not stable throughout tumour progression in breast cancer. Prognostic information for individual patients appears to be available from the analysis of biomarker expression in synchronous metastatic lymph nodes. The study supports biomarker analysis also in asynchronous relapses.

Place, publisher, year, edition, pages
Springer Verlag (Germany), 2013
Keywords
Breast cancer, Lymph node metastases, Relapse, Prognosis, Tumour progression, St Gallen molecular subtypes
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-95949 (URN)10.1007/s10549-013-2617-8 (DOI)000321588900009 ()
Note

Funding Agencies|Swedish Breast Cancer Organisation (BRO)||Swedish Cancer Society||Swedish Research Council||Gunnar Nilsson Cancer Foundation||Mrs. Berta Kamprad Foundation||Stig and Ragna Gorthons Stiftelse||Skane County Councils Research and Development Foundation||Governmental Funding of Clinical Research within the National Health Service (ALF)||

Available from: 2013-08-19 Created: 2013-08-12 Last updated: 2017-12-06
Shabo, I., Olsson, H., Stål, O. & Svanvik, J. (2013). Breast Cancer Expression of DAP12 is Associated With Skeletal and Liver Metastases and Poor Survival. Clinical Breast Cancer, 13(5), 371-377
Open this publication in new window or tab >>Breast Cancer Expression of DAP12 is Associated With Skeletal and Liver Metastases and Poor Survival
2013 (English)In: Clinical Breast Cancer, ISSN 1526-8209, E-ISSN 1938-0666, Vol. 13, no 5, p. 371-377Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2013
Keywords
Cell fusion, Tumor-associated macrophages, Tissue-specific metastasis, Tumor immunology, Tumor microenvironment
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-98662 (URN)10.1016/j.clbc.2013.05.003 (DOI)000324341600010 ()
Note

Funding Agencies|County Council of Ostergotland||

Available from: 2013-10-10 Created: 2013-10-10 Last updated: 2017-12-06
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