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. 2017 Apr 29;8(33):54592-54603.
doi: 10.18632/oncotarget.17523. eCollection 2017 Aug 15.

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

Theresa Link  1   2   3 , Friederike Kuithan  4 , Armin Ehninger  5   6 , Jan Dominik Kuhlmann  1   2   3 , Michael Kramer  5 , Andreas Werner  7 , Axel Gatzweiler  8 , Barbara Richter  9 , Gerhard Ehninger  2   3   5 , Gustavo Baretton  4 , Michael Bachmann  2   3   10   11 , Pauline Wimberger  1   2   3 , Katrin Friedrich  4
Affiliations

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

Theresa Link et al. Oncotarget. .

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.

Keywords: HER2/neu; PSCA; breast cancer; therapeutic target.

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Conflict of interest statement

CONFLICTS OF INTERESTS AE, GE and MB hold patents related to an anti-PSCA antibody. The remaining authors declare that no conflict of interest exists.

Figures

Figure 1
Figure 1. Compartmental distribution of PSCA-expression in breast cancer tissue
The Figure shows representative immunohistological PSCA-staining results in (A) malignant breast cancer tissue including tumor stroma and (B) in non-neoplastic breast tissue. Besides membranous and cytoplasmatic expression of PSCA in invasive breast cancer cells, PSCA-expression is completely absent in stromal cells and in non-neoplastic breast tissue.
Figure 2
Figure 2. PSCA-expression levels in breast cancer tissue
The Figure shows a representative immunohistological PSCA-staining in malignant breast cancer tissue. Among the studied breast cancer patients, PSCA-expression was detected (A) in only a few disseminated tumor cells with weak intensity, referred to as “low expression” or (B) in a high number of invasive tumor cells, referred to as “high expression”.
Figure 3
Figure 3. PSCA-expression in breast cancer and its association with HER2/neu status
(A) The pie chart shows the proportion of low and high PSCA-expression among the studied breast cancer patients according to TMA-analysis. (B) The stacked columns show the relative distribution of HER2/neu positive and HER2/neu negative patients with regard to the PSCA-status. Absolute patient numbers of each subgroup are indicated.
Figure 4
Figure 4. Prognostic relevance of PSCA-expression in the total breast cancer population
The Kaplan-Meier plots show (A) progression-free survival and (B) overall survival of the total study population with PSCA-positive (red curves) vs. PSCA-negative tumors (black curves).
Figure 5
Figure 5. Prognostic relevance of PSCA-expression in HER2/neu positive breast cancer patients
The Kaplan-Meier plots show (A) progression-free survival and (B) overall survival of HER2/neu positive breast cancer patients with PSCA-positive (dark-green curves) vs. PSCA-negative tumors (olive-green curves).
Figure 6
Figure 6. Prognostic relevance of PSCA-expression in breast cancer patients with intermediate risk
The Kaplan-Meier plots show (A) progression-free survival and (B) overall survival of intermediate risk breast cancer patients with PSCA-positive (dark-green curves) vs. PSCA-negative tumors (olive-green curves).
See this image and copyright information in PMC

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