A60
Androgen receptor expression in epithelial ovarian cancer decreases after exposure to chemotherapy: an immunohistochemical study
Ahmed Elattar1, Craig N Robson1, Paul Cross2, Richard J Edmondson1
1Northern Institute of Cancer Research, Newcastle University, UK, 2Northern Gynaecological Oncology Centre, Queen Elizabeth Hospital, Gateshead, Newcastle, UK
Background
Epithelial ovarian cancer (EOC) often arises from ovarian surface epithelium (OSE), both of which express the androgen receptor (AR). Androgenic stimulation of OSE and ovarian cancer cell lines results in increased proliferation and protection from apoptosis. Nevertheless, in clinical trials anti-androgens have had a low objective response rate (4-6%) in relapsed ovarian cancer. In the present study we explore the effects of exposure to chemotherapy on androgen receptor expression as a potential mechanism for anti-androgen poor response rate.
Objective
To identify the effect of chemotherapy on androgen receptor expression in primary epithelial ovarian cancer.
Results
Paired pre- and post-chemotherapy histological samples from 30 patients were incorporated into a tissue microarray (TMA). The TMA was stained for AR using immunohistochemical techniques. AR expression using a modified H-score for assessment of cellular staining was found to decrease significantly after the tumour was treated with chemotherapy. Prior to chemotherapy, 9 cases did not express nuclear AR. The mean nuclear AR expression decreased from 8.2 before chemotherapy to 4.6 after chemotherapy (P = 0.018). The mean cytoplasmic AR expression decreased significantly from 13.2 before chemotherapy to 10 after chemotherapy (P = 0.01).
Conclusion
Adjuvant chemotherapy results in a reduction in androgen receptor expression. Anti-androgen use early in the course of ovarian cancer is more likely to be effective as androgen receptor expression decreases with exposure to chemotherapy and this may explain the low response rates seen in clinical trials of heavily pre-treated patients. Further studies are needed to explore the role of AR expression by immunohistochemistry as a potential test to select patients for anti-androgen therapy.
