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Thorstenson, Sten
Publications (10 of 14) Show all publications
Lundström, C., Thorstenson, S., Waltersson, M., Persson, A. & Treanor, D. (2015). Summary of 2nd Nordic symposium on digital pathology. Journal of Pathology Informatics, 6
Open this publication in new window or tab >>Summary of 2nd Nordic symposium on digital pathology
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2015 (English)In: Journal of Pathology Informatics, ISSN 2229-5089, E-ISSN 2153-3539, Vol. 6Article in journal, Editorial material (Refereed) Published
Abstract [en]

Techniques for digital pathology are envisioned to provide great benefits in clinical practice, but experiences also show that solutions must be carefully crafted. The Nordic countries are far along the path toward the use of whole-slide imaging in clinical routine. The Nordic Symposium on Digital Pathology (NDP) was created to promote knowledge exchange in this area, between stakeholders in health care, industry, and academia. This article is a summary of the NDP 2014 symposium, including conclusions from a workshop on clinical adoption of digital pathology among the 144 attendees.

Place, publisher, year, edition, pages
Medknow Publications, 2015
National Category
Other Medical Engineering
Identifiers
urn:nbn:se:liu:diva-118879 (URN)10.4103/2153-3539.151889 (DOI)25774316 (PubMedID)
Funder
VINNOVA
Available from: 2015-06-04 Created: 2015-06-04 Last updated: 2017-12-04
Thorstenson, S., Molin, J. & Lundström, C. (2014). Implementation of large‑scale routine diagnostics using whole slideimaging in Sweden: Digital pathology experiences 2006-2013. Journal of Pathology Informatics, 5(14)
Open this publication in new window or tab >>Implementation of large‑scale routine diagnostics using whole slideimaging in Sweden: Digital pathology experiences 2006-2013
2014 (English)In: Journal of Pathology Informatics, ISSN 2229-5089, E-ISSN 2153-3539, Vol. 5, no 14Article in journal (Refereed) Published
Abstract [en]

Recent technological advances have improved the whole slide imaging (WSI) scanner quality and reduced the cost of storage, thereby enabling the deployment of digital pathology for routine diagnostics. In this paper we present the experiences from two Swedish sites having deployed routine large-scale WSI for primary review. At Kalmar County Hospital, the digitization process started in 2006 to reduce the time spent at the microscope in order to improve the ergonomics. Since 2008, more than 500,000 glass slides have been scanned in the routine operations of Kalmar and the neighboring Linköping University Hospital. All glass slides are digitally scanned yet they are also physically delivered to the consulting pathologist who can choose to review the slides on screen, in the microscope, or both. The digital operations include regular remote case reporting by a few hospital pathologists, as well as around 150 cases per week where primary review is outsourced to a private clinic. To investigate how the pathologists choose to use the digital slides, a web-based questionnaire was designed and sent out to the pathologists in Kalmar and Linköping. The responses showed that almost all pathologists think that ergonomics have improved and that image quality was sufficient for most histopathologic diagnostic work. 38 ± 28% of the cases were diagnosed digitally, but the survey also revealed that the pathologists commonly switch back and forth between digital and conventional microscopy within the same case. The fact that two full-scale digital systems have been implemented and that a large portion of the primary reporting is voluntarily performed digitally shows that large-scale digitization is possible today.

Keywords
Clinical routine, digital pathology, digital pathology workflow, remote work, whole slide imaging
National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:liu:diva-107497 (URN)10.4103/2153-3539.129452 (DOI)24843825 (PubMedID)
Funder
Swedish Research Council, 2011-4138VINNOVA, 2012-01121
Available from: 2014-06-13 Created: 2014-06-13 Last updated: 2017-12-05
Nilsson, C., Koliadi, A., Johansson, I., Ahlin, C., Thorstenson, S., Bergkvist, L., . . . Fjallskog, M.-L. (2013). High proliferation is associated with inferior Outcome in male breast cancer patients. Modern Pathology, 26(1), 87-94
Open this publication in new window or tab >>High proliferation is associated with inferior Outcome in male breast cancer patients
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2013 (English)In: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 26, no 1, p. 87-94Article in journal (Refereed) Published
Abstract [en]

Assessment of proliferation is important in female breast cancer and individual treatment decisions are based upon its results, especially in the lumina! subgroups. Gene expression analyses fail to group male breast cancer into the intrinsic subgroups previously established in female breast cancer. Even though proliferation has been shown to divide male breast cancer into molecular subgroups with different prognoses, the clinical importance of proliferation markers has not yet been elucidated. Previous studies in male breast cancer have demonstrated contradictory results regarding the prognostic impact of histological grade and Ki-67, parameters strongly associated with proliferation. The aim of the present project was to study proliferation in male breast cancer by assessing other proliferation-related markers viz. cyclins A, B, D1 and mitotic count. A total of 197 male breast cancer cases with accessible paraffin-embedded material and outcome data were investigated. Immunohistochemical stainings were performed on tissue microarrays. Kaplan-Meier estimates and the Cox proportional regression models were used for survival analyses with breast cancer death as the event. The subset of patients with high expression of cyclin A (hazard ratio (HR) 3.7; P=0.001) and B (HR 2.7; P=0.02) demonstrated a poorer survival. Furthermore, high mitotic count was associated with an increased risk of breast cancer death (HR 2.5; P=0.01). In contrast, cyclin D1 overexpression was predictive of better breast cancer survival (HR 0.3; P=0.001). In conclusion, high levels of cyclin A and B expression and an elevated mitotic count result in a two to threefold higher risk for breast cancer death, whereas cyclin D1 overexpression halves the risk. The clinical utility of these proliferation markers needs further elucidation. Modern Pathology (2013) 26, 87-94; doi:10.1038/modpathol.2012.145; published online 24 August 2012

Place, publisher, year, edition, pages
Nature Publishing Group, 2013
Keywords
breast cancer, immunohistochemistry, male
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-88461 (URN)10.1038/modpathol.2012.145 (DOI)000313306900010 ()
Note

Funding Agencies|Regional Research Foundation in Uppsala-Orebro||Lions Cancer Foundation||University Hospital||Uppsala and Vastmanlands Research Foundation||

Available from: 2013-02-07 Created: 2013-02-07 Last updated: 2017-12-06
Nilsson, C., Johansson, I., Ahlin, C., Thorstenson, S., Amini, R.-M., Holmqvist, M., . . . Fjallskog, M.-L. (2013). Molecular subtyping of male breast cancer using alternative definitions and its prognostic impact. Acta Oncologica, 52(1), 102-109
Open this publication in new window or tab >>Molecular subtyping of male breast cancer using alternative definitions and its prognostic impact
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2013 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 1, p. 102-109Article in journal (Refereed) Published
Abstract [en]

Background. Male breast cancer (MBC) is an uncommon disease and there is limited information on the prognostic impact of routinely used clinicopathological parameters. Material and methods. In a retrospective setting, we reviewed 197 MBC patients with accessible paraffin-embedded tumor tissue and clinicopathological data. Immunohistochemical (IHC) stainings were performed on tissue microarrays and histological grading on conventional slides. Cox proportional regression models were applied for uni- and multivariate analyses using breast cancer death as the event. Results. Estrogen receptor (ER) and progesterone receptor positivity were demonstrated in 93% and 77% of patients, respectively. Nottingham histologic grade (NHG) III was seen in 41% and HER2 positivity in 11%. Classification into molecular subtypes using IHC markers according to three alternative definitions revealed luminal A and luminal B in 81% vs. 11%; 48% vs. 44% and 41% vs. 42% of cases. Two cases of basal-like were identified, but no cases of HER2-like. Factors associated with an increased risk of breast cancer death were node positivity (HR 4.5; 95% CI 1.8-11.1), tumor size andgt;20 mm (HR 3.3; 95% CI 1.4-7.9) and ER negativity (HR 10.9; 95% CI 3.2-37.9). No difference in breast cancer death between the luminal subgroups was demonstrated, regardless of definition. Conclusion. MBC tumors were more often of high grade, whereas HER2 overexpression was as frequent as in FBC. Lymph nodes, tumor size and ER status were independent predictors of breast cancer death. The prognostic impact of molecular subtyping in MBC seems to differ from that previously established in FBC.

Place, publisher, year, edition, pages
Informa Healthcare, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-88364 (URN)10.3109/0284186X.2012.711952 (DOI)000312505900013 ()
Note

Funding Agencies|Regional Research Foundation in Uppsala-Orebro||Lions Cancer Foundation||University Hospital, Uppsala||Vastmanlands Research Foundation||

Available from: 2013-02-04 Created: 2013-02-04 Last updated: 2017-12-06
Arlehag, L., Adell, G., Knutsen Holmqvist, A., Thorstenson, S. & Sun, X.-F. (2005). ATM expression in rectal cancers with or without preoperative radiotherapy. Oncology Reports, 14(2), 313-317
Open this publication in new window or tab >>ATM expression in rectal cancers with or without preoperative radiotherapy
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2005 (English)In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 14, no 2, p. 313-317Article in journal (Refereed) Published
Abstract [en]

Patients with ATM (Ataxia-Telangiectasia mutated) mutation show increased sensitivity to radiation and have a higher risk of developing malignancies. The present study aimed to investigate whether ATM expression was related to radiotherapy, and clinicopathological and biological variables in rectal cancers. ATM expression was immunohistochemically examined in 78 rectal cancers from patients who participated in a Swedish rectal cancer trial of preoperative radiotherapy. Of 78 patients, 44 underwent surgery alone, and 34 underwent both preoperative radiotherapy and surgery. Fifty-eight cases had normal rectal mucosa adjacent to the tumour. The results showed that, compared to normal mucosa, tumours had less nuclear (p=0.03) but more cytoplasmic expression of ATM (p=0.004). In tumours, less expression of ATM, either in the nucleus (p=0.07) or in the cytoplasm (p=0.02 for staining intensity, and p=0.07 for staining percentage), tended to be correlated with male patients. Also, ATM expression was not related to radiotherapy or other clinicopathological and biological variables (p > 0.05). In conclusion, the pattern of ATM expression was changed from normal mucosa to tumour. Less expression of ATM may be related to males.

Keywords
ATM, immunohistochemistry, radiotherapy, rectal cancer
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-48197 (URN)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12
Razavi, A. R., Gill, H., Stål, O., Sundquist, M., Thorstenson, S., Åhlfeldt, H., . . . The South-East Swedish Breast Cancer Study Group, . (2005). Exploring cancer register data to find risk factors for recurrence of breast cancer: Application of Canonical Correlation Analysis. BMC Medical Informatics and Decision Making, 5(29), 29-35
Open this publication in new window or tab >>Exploring cancer register data to find risk factors for recurrence of breast cancer: Application of Canonical Correlation Analysis
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2005 (English)In: BMC Medical Informatics and Decision Making, ISSN 1472-6947, Vol. 5, no 29, p. 29-35Article in journal (Refereed) Published
Abstract [en]

Background

A common approach in exploring register data is to find relationships between outcomes and predictors by using multiple regression analysis (MRA). If there is more than one outcome variable, the analysis must then be repeated, and the results combined in some arbitrary fashion. In contrast, Canonical Correlation Analysis (CCA) has the ability to analyze multiple outcomes at the same time.

One essential outcome after breast cancer treatment is recurrence of the disease. It is important to understand the relationship between different predictors and recurrence, including the time interval until recurrence. This study describes the application of CCA to find important predictors for two different outcomes for breast cancer patients, loco-regional recurrence and occurrence of distant metastasis and to decrease the number of variables in the sets of predictors and outcomes without decreasing the predictive strength of the model.

Methods

Data for 637 malignant breast cancer patients admitted in the south-east region of Sweden were analyzed. By using CCA and looking at the structure coefficients (loadings), relationships between tumor specifications and the two outcomes during different time intervals were analyzed and a correlation model was built.

Results

The analysis successfully detected known predictors for breast cancer recurrence during the first two years and distant metastasis 2–4 years after diagnosis. Nottingham Histologic Grading (NHG) was the most important predictor, while age of the patient at the time of diagnosis was not an important predictor.

Conclusion

In cancer registers with high dimensionality, CCA can be used for identifying the importance of risk factors for breast cancer recurrence. This technique can result in a model ready for further processing by data mining methods through reducing the number of variables to important ones.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-12706 (URN)10.1186/1472-6947-5-29 (DOI)
Available from: 2009-02-22 Created: 2008-10-24 Last updated: 2009-03-10Bibliographically approved
Ryden, L., Jirstrom, K., Bendahl, P., Ferno, M., Nordenskjöld, B., Stål, O., . . . Landberg, G. (2005). Tumor-specific expression of vascular endothelial growth factor receptor 2 but not vascular endothelial growth factor or human epidermal growth factor receptor 2 is associated with impaired response to adjuvant tamoxifen in premenopausal breast cancer. Journal of Clinical Oncology, 23(21), 4695-4704
Open this publication in new window or tab >>Tumor-specific expression of vascular endothelial growth factor receptor 2 but not vascular endothelial growth factor or human epidermal growth factor receptor 2 is associated with impaired response to adjuvant tamoxifen in premenopausal breast cancer
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2005 (English)In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 23, no 21, p. 4695-4704Article in journal (Refereed) Published
Abstract [en]

Purpose Vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) are often coexpressed in breast cancer, and potentially affect cellular pathways and key proteins such as the estrogen receptor (ER) targeted by endocrine treatment. We therefore explored the association between adjuvant tamoxifen treatment in breast cancer and expression of VEGF-A and VEGFR2, as well as human epidermal growth factor receptor 2 (HER2), which represents a candidate gene product involved in tamoxifen resistance.

Patients and Methods Immunohistochemical expression of tumor-specific VEGF-A, VEGFR2, and HER2 was evaluated in tumor specimens from premenopausal breast cancer patients randomly assigned to 2 years of tamoxifen or no treatment (n = 564), with 14 years of follow-up. Hormone receptor status was determined in 96% of the tumors.

Results VEGF-A, VEGFR2, and HER2 were assessable in 460, 472, and 428 of the tumors, respectively. In patients with ER–positive and VEGFR2-low tumors, adjuvant tamoxifen significantly increased recurrence-free survival (RFS; [HR] hazard ratio for RFS, 0.53; P = .001). In contrast, tamoxifen treatment had no effect in patients with VEGFR2-high tumors (HR for RFS, 2.44; P = .2). When multivariate interaction analyses were used, this difference in treatment efficacy relative to VEGFR2 expression status was statistically significant for both ER-positive (P = .04) plus ER-positive and progesterone receptor–positive tumors. We found no significant difference in tamoxifen treatment effects in relation to VEGF-A or HER2 status.

Conclusion Tumor-specific expression of VEGFR2 was associated with an impaired tamoxifen effect in hormone receptor–positive premenopausal breast cancer. Tamoxifen in combination with VEGFR2 inhibitors might be a novel treatment approach for VEGFR2-expressing breast cancer, and such a treatment might restore the tamoxifen response.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-46084 (URN)10.1200/JCO.2005.08.126 (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13
Rydén, L., Jönsson, P.-E., Chebil, G., Dufmats, M., Fernö, M., Jirström, K., . . . Nordenskjöld, B. (2005). Two years of adjuvant tamoxifen in premenopausal patients with breast cancer: a randomised, controlled trial with long-term follow-up. European Journal of Cancer, 41(2), 256-264
Open this publication in new window or tab >>Two years of adjuvant tamoxifen in premenopausal patients with breast cancer: a randomised, controlled trial with long-term follow-up
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2005 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 41, no 2, p. 256-264Article in journal (Refereed) Published
Abstract [en]

Adjuvant tamoxifen treatment increases recurrence-free survival (RFS) and overall survival (OS) in early breast cancer, although in premenopausal patients the number of studies comparing tamoxifen vs no treatment are limited. We report herein the effect on RFS of adjuvant tamoxifen treatment in a multicentre trial of premenopausal patients with stage II breast cancer patients randomised between 1986 and 1991 to 2 years of tamoxifen treatment (n = 276) or no treatment (n = 288). The receptor status of the tumour was known for 541 (96%) of the patients included. Tamoxifen treatment significantly increased RFS in patients with hormone receptor-positive (oestrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+)) tumours (Relative Risk (RR) 0.65; 95% Confidence Interval (CI): 0.48–0.89, P = 0.006), and the beneficial effect of tamoxifen was extended to patients with indicators of poor prognosis, such as young age and nodal-positivity. PR status was a significant predictor of response to tamoxifen in multivariate models with testing of interactions of hormone receptor status and adjuvant therapy.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24443 (URN)10.1016/j.ejca.2004.06.030 (DOI)6551 (Local ID)6551 (Archive number)6551 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
Sundquist, M., Thorstenson, S., Brudin, L., Wingren, S. & Nordenskjöld, B. (2002). Incidence and prognosis in early onset breast cancer. Breast, 11(1), 30-35
Open this publication in new window or tab >>Incidence and prognosis in early onset breast cancer
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2002 (English)In: Breast, ISSN 0960-9776, E-ISSN 1532-3080, Vol. 11, no 1, p. 30-35Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to assess the incidence and prognosis in early onset breast cancer. Age-adjusted incidence and death rate for the 5394 Swedish women diagnosed with breast cancer under the age of 40 between 1960 and 1996 was studied using data from the Swedish Cancer Registry and Swedish Death Cause Registry. A total of 107 consecutive young patients with invasive breast cancer undergoing surgery during 1980–1993 in the Southeast Swedish health care region were retrospectively followed up and their cancers reviewed and graded blindly. The median follow-up time was 11.2 years. The applicability of the Nottingham Prognostic Index (NPI) as a prognostic tool was investigated. Grade, age, node status, tumour size, S-phase fraction and steroid receptor content were related to survival univariately and multivariately in a Cox proportional hazard analysis.

The incidence of early onset breast cancer has increased moderately and the survival rate has not improved during the last 35 years. When young women are diagnosed with breast cancer their tumours are larger, their lymph nodes more often involved, and the median grade higher than in older with 64% having grade 3 tumours. Lymph node status was the strongest sole prognostic indicator but the use of NPI gave more accurate prognostic information than node status alone.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-28170 (URN)10.1054/brst.2001.0358 (DOI)12986 (Local ID)12986 (Archive number)12986 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
Gentile, M., Wiman, Å., Thorstenson, S., Loman, N., Borg, Å. & Wingren, S. (2001). Deletion mapping of chromosome segment 11q24-q25, exhibiting extensive allelic loss in early onset breast cancer. International Journal of Cancer, 92(2), 208-213
Open this publication in new window or tab >>Deletion mapping of chromosome segment 11q24-q25, exhibiting extensive allelic loss in early onset breast cancer
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2001 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 92, no 2, p. 208-213Article in journal (Refereed) Published
Abstract [en]

Frequent allelic deletions at chromosome 11q24-q25 have been described in both early and late onset breast cancers, suggesting the existence of a gene locus implicated in the initiation and/or progression of the disease. In the present study we fine mapped this region further by loss of heterozygosity (LOH) analysis in a population of early onset breast cancer cases (n = 102, 22 to 36 years old). Loss of chromosomal material was assessed for possible association with patient survival as well as Nottingham histologic grade (NHG). Additionally, we investigated the involvement of the 11q24-q25 locus in a group of familial breast cancer cases with no detectable BRCA1 or BRCA2 gene alterations (n = 32, ages 28 to 40 years). Among the consecutive patients, extensive LOH was observed for all markers at 11q24-q25, with frequencies ranging from 42% to 54%. Deletion at the D11S4125 marker was found to be associated with reduced survival (p = 0.026), whereas the adjacent D11S387 marker correlated with higher histologic grade (p = 0.042). In the familial cases, the most telomeric markers showed substantially lower proportions of LOH, ranging from 10% to 21%. Comparison of the two patient groups demonstrated that this difference in LOH frequency was statistically significant for the D11S4098, D11S968, D11S387 and D11S4125 markers (p = 0.020, p = 0.029, p = 0.0070 and p = 0.0030, respectively). We conclude that 11q25 may harbor a gene implicated in early onset breast cancer. Our data suggest that the most probable position for this locus is defined by the markers D11S387 and D11S4125 and furthermore that it may play a less significant role in familial breast cancer cases not linked to either of the BRCA genes.

Keywords
11q, LOH, early onset, familial breast cancer, prognosis, young age
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-49326 (URN)10.1002/1097-0215(200102)9999:9999<::AID-IJC1169>3.0.CO;2-4 (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12Bibliographically approved
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