Translational research in the Gynecologic Oncology Group: Evaluation of ovarian cancer markers, profiles, and novel therapies

Objectives: To review the translational research (TR) performed in the Gynecologic Oncology Group (GOG) to evaluate ovarian cancer markers, profiles and novel therapies. Methods: Prospective trials with stand alone or embedded TR objectives involving patient and specimen accrual as well as retrospective studies using banked specimens and resources were and continue to be performed in the GOG. Appropriate statistical methods are employed to evaluate associations with clinical characteristics and outcomes including tumor response, adverse events, progression free survival and overall survival. Results: Highlights are presented for some of the collaborative and multidisciplinary TR conducted with the GOG to evaluate markers, pathway and novel therapeutics in epithelial ovarian, primary peritoneal and/or fallopian tube cancer. For example, in GOG 111, high immunohistochemical (IHC) expression of cyclin E was associated with a shorter median survival (29 versus 35 months) and an increased risk of death (hazard ratio [HR]=1.4, 95% confidence interval [CI]=1.0-2.1, p=0.05). In GOG 114/132, non-detectable immunoblot expression of maspin was associated with debulking status (p=0.034) and an increased risk of disease progression (HR=1.89, 95% CI=1.04-3.45, p=0.038) and death (HR=1.99, 95% CI=1.07-3.69, p=0.030) while high CD105-microvessel density (MVD), but not CD31-MVD in tumor was associated with increased risk of disease progression (HR=1.873, 95% CI=1.102-3.184, p=0.020) but not death. In GOG 172, low IHC expression of BRCA1 was associated with advanced stage (p<0.001), serous histology (p<0.001) and a reduced risk of disease progression (HR=0.64, 95% CI=0.42-0.96) and death (HR=0.51, 95% CI=0.32-0.83) while the CA/AA versus CC genotypes in C8092A in ERCC1 were associated with an increased risk of disease progression (HR=1.44, 95% CI=1.06-1.94, p=0.018) and death (HR=1.50, 95% CI=1.07-2.09, p=0.018). Conclusions: The GOG has an extensive TR program that provides clues regarding the molecular and biochemical mechanisms of disease, treatments and outcomes in women with or at risk for a gynecologic malignancy.