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Androgen Mediation of Thrombocytosis in Epithelial Ovarian Cancer Biology

Authors' Affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California

Requests for reprints: Andrew John Li, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite 160 West, Los Angeles, CA 90048. Phone: 310-423-3599; Fax: 310-423-0155; E-mail: Andrew.Li{at}cshs.org.

Purpose: Preoperative thrombocytosis (platelet count > 400 x 10⁹/L) at initial exploration for epithelial ovarian carcinoma is associated with decreased surgical cytoreducibility and poor survival. Platelets express androgen receptor (AR), which contains a polymorphic CAG trinucleotide repeat sequence of which the length inversely correlates with AR transactivation function. We hypothesized that androgen-mediated thrombocytosis promotes aggressive ovarian cancer biology.

Experimental Design: Sixty-three patients with epithelial ovarian carcinoma underwent genotype analysis of the CAG repeat polymorphism in AR. Medical records were reviewed to assess preoperative thrombocytosis, surgical findings, and survival. Data were examined using the Fisher's exact, logistic regression, and Kaplan-Meier analyses.

Results: AR CAG repeat lengths ranged from 8 to 27, with a median of 23. Fifteen of 63 patients (23.8%) showed preoperative thrombocytosis. Short AR allelotype ( 20 CAG repeats) was associated with a higher incidence of thrombocytosis (P = 0.04). The combination of short AR allelotype and thrombocytosis was the only significant factor that predicted inability to achieve optimal surgical cytoreduction (P = 0.02). Women with short AR allelotype and thrombocytosis showed statistically decreased progression-free survival (13 versus 37 months, P = 0.01) and overall survival (37 versus 65 months, P = 0.02) when compared with women with long AR allelotype and normal platelet counts. On multivariate analyses, suboptimal cytoreduction was the only significant factor predictive of disease-specific overall survival (P = 0.0002) but the combination of short AR allelotype and thrombocytosis approached statistical significance (P = 0.08).

Conclusions: Androgen modulation of thrombocytosis may promote aggressive epithelial ovarian cancer biology.