Oncotarget

Research Papers:

Exploratory investigation of PSCA-protein expression in primary breast cancer patients reveals a link to HER2/neu overexpression

Theresa Link, Friederike Kuithan, Armin Ehninger, Jan Dominik Kuhlmann _, Michael Kramer, Andreas Werner, Axel Gatzweiler, Barbara Richter, Gerhard Ehninger, Gustavo Baretton, Michael Bachmann, Pauline Wimberger and Katrin Friedrich

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Oncotarget. 2017; 8:54592-54603. https://doi.org/10.18632/oncotarget.17523

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Abstract

Theresa Link1,2,3, Friederike Kuithan4, Armin Ehninger5,6, Jan Dominik Kuhlmann1,2,3, Michael Kramer5, Andreas Werner7, Axel Gatzweiler8, Barbara Richter9, Gerhard Ehninger2,3,5, Gustavo Baretton4, Michael Bachmann2,3,10,11, Pauline Wimberger1,2,3 and Katrin Friedrich4

1Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

2National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany

3German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany

4Department of Pathology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

5Medizinische Klinik und Poliklinik I, Medical Faculty and University Hospital, Technische Universität Dresden, Dresden, Germany

6GEMoaB Monoclonals GmbH, Dresden, Germany

7Department of Gynecology, Diakonissenkrankenhaus Dresden, Dresden, Germany

8Department of Gynecology, St. Joseph Stift, Dresden, Germany

9Department of Gynecology, Elblandkliniken, Dresden, Germany

10University Cancer Center (UCC) Carl Gustav Carus, Tumor Immunology, Technische Universität Dresden, Dresden, Germany

11Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany

Correspondence to:

Jan Dominik Kuhlmann, email: [email protected]

Keywords: breast cancer, PSCA, HER2/neu, therapeutic target

Received: November 09, 2016    Accepted: March 29, 2017    Published: April 29, 2017

ABSTRACT

Background: Prostate stem cell antigen (PSCA) has been suggested as biomarker and therapeutic target for prostate cancer. Recent advances showed that PSCA is up-regulated in other cancer entities, such as bladder or pancreatic cancer. However, the clinical relevance of PSCA-expression in breast cancer patients has not yet been established and is therefore addressed by the current study.

Methods: PSCA-protein expression was assessed in 405 breast cancer patients, using immunohistochemistry (PSCA antibody MB1) and tissue microarrays.

Results: PSCA-expression was detected in 94/405 patients (23%) and correlated with unfavorable histopathological grade (p=0.011) and increased Ki67 proliferation index (p=0.006). We observed a strong positive correlation between PSCA-protein expression and HER2/neu receptor status (p<0.001). PSCA did not provide prognostic information in the analyzed cohort. Interestingly, the distribution of PSCA-expression among triple negative patients was comparable to the total population.

Conclusion: We identified a subgroup of PSCA-positive breast cancer patients, which could be amenable for a PSCA-targeted therapy. Moreover, given that we found a strong positive correlation between PSCA- and HER/neu expression, targeting PSCA may provide an alternative therapeutic option in case of trastuzumab resistance.


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