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Short Androgen Receptor Allele Length Is a Poor Prognostic Factor in Epithelial Ovarian Carcinoma¹

Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California 90048

Purpose: Epidemiological evidence implicates a heightened androgenic state in women with epithelial ovarian cancer. Androgen activity may be modulated by altered expression or activity of the androgen receptor (AR) or AR polymorphisms. Exon 1 of the AR gene contains a polymorphic (CAG)_n sequence whose length is inversely correlated with transcriptional activity.

Experimental Design: Differential expression of AR mRNA and protein was examined in 46 primary cultures of normal human ovarian surface epithelium (HOSE) and malignant Cedars-Sinai ovarian cancer (CSOC) ovarian epithelial cells. AR allele length was characterized by genotyping in 77 ovarian cancer specimens.

Results: AR mRNA expression was higher in CSOC primary cultures (1.58 ± 0.17) when compared with HOSE (1 ± 0.09, P = 0.005), but protein expression was not statistically different. CAG repeat lengths were shorter in CSOC (20.6 ± 1.2) than in HOSE (23.4 ± 0.9, P = 0.04). Patients with an AR allele containing 19 CAG repeats had a shorter time to recurrence (5.5 versus 19.4 months, P < 0.0001) and overall survival (9 versus 32.6 months, P = 0.0007). There was no correlation between AR allelotype and age of diagnosis, stage, or grade; however, a short CAG length 19 repeats was associated with decreased surgical cytoreducibility (44.4 versus 10.3%, P = 0.035). Multivariate analyses confirmed a short AR allele as an independent prognostic factor (P = 0.02).

Conclusions: These data support epidemiological evidence linking heightened androgenicity to the pathogenesis and tumor biology of epithelial ovarian cancer.

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