Increased androgen receptor expression in serous carcinoma of the ovary is associated with an improved survival

Abstract

BackgroundAltered androgen hormone homeostasis and androgen receptor (AR) activity have been implicated in ovarian carcinogenesis but the relationship between AR expression in ovarian cancer and clinical outcome remains unclear.MethodsIn this study, the prognostic impact of AR expression was investigated using immunohistochemistry in tissue microarrays from 154 incident cases of epithelial ovarian cancer (EOC) in the prospective, population-based cohorts Malmö Diet and Cancer Study and Malmö Preventive Project. A subset of corresponding fallopian tubes (n = 36) with no histopathological evidence of disease was also analysed.ResultsWhile abundantly expressed in the majority of fallopian tubes with more than 75% positive nuclei in 16/36 (44%) cases, AR was absent in 108/154 (70%) of EOC cases. AR expression was not related to prognosis in the entire cohort, but in the serous subtype (n = 90), AR positivity (> 10% positive nuclei) was associated with a prolonged disease specific survival in univariate (HR= 0.49; 95% CI 0.25-0.96; p= 0.038) and multivariate (HR= 0.46; 95% CI 0.22-0.97; p= 0.042) analysis, adjusted for age, grade and clinical stage.ConclusionsAR expression is considerably reduced in EOC as compared to fallopian tubes, and in EOC of the serous subtype, high AR expression is a favourable prognostic factor. These results indicate that assessment of AR expression might be of value for treatment stratification of EOC patients with serous ovarian carcinoma.

Prognostic Significance of Hormonal Receptor Status of Malignant Ovarian Tumors

“…On the other hand, results of our study contradict the data of the other studies which have determined that high expression of androgen receptors is a favorable prognostic factor in patients with serous OC [30,44].…”

Predicting time to ovarian carcinoma recurrence using protein markers

“…AR expression was a favorable prognostic factor for survival, and malignant transformation was found to involve downregulation of AR in patients with epithelial ovarian cancer. No differences in AR expression were observed between primary and metastatic ovarian tumors, suggesting that downregulation of AR occurs during early carcinogenesis (29). Transcriptome-based predictive analysis of treatment response in breast cancer has been shown to be highly accurate by multiple gene signatures.…”

“…Although only the androgen receptor (AR) protein was found in both signatures, a similarity in protein expression profiles was observed between the 2 sets of markers by hierarchical cluster analysis. Presurgical androgen-deprivation therapy is first-line therapy in nonmetastatic prostate cancer (27), and the impact of AR expression in ovarian carcinoma has been the subject of several studies (28)(29)(30). AR expression was a favorable prognostic factor for survival, and malignant transformation was found to involve downregulation of AR in patients with epithelial ovarian cancer.…”

Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition

“…31 However, AR expression in serous carcinomas was associated with improved survival in one study (n 5 90). 35 Androgens may have a direct impact on ovarian carcinogenesis, or act via their function as precursors to estrogens. Androstenedione is the preferential substrate for aromatase, and higher androstenedione synthesis may lead to an increased synthesis of estrogens.…”

“…An incidence density sampling protocol was used, such that controls could include subjects who became a case later in time and each control could be sampled more than once. Cases and controls in both study phases were matched on: study recruitment center, age at blood donation (66 months), time of the day of blood collection (61 h), fasting status (<3 h, 3-6 h, >6 h), and menopausal status at blood collection (premenopausal, perimenopausal, postmenopausal), as well as menstrual cycle phase for premenopausal women ("early follicular" (days 0-7 of the cycle), "late follicular" (days 8-11), "peri-ovulatory" (days 12-16), "mid-luteal" (days [20][21][22][23][24], and "other luteal" (days 17-19 or days [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. Cases missing data on phase of menstrual cycle were matched to controls with missing information on menstrual cycle phase.…”