Cyclin D1 and p57 expression in advanced ovarian epithelial carcinoma: A GOG study.

Abstract

5086 Background:The aim of this study was to investigate expression of cyclin D1 and p57 in advanced epithelial ovarian cancer and their association with progression free survival (PFS), overall survival (OS), clinical response and evidence of disease at second look laparotomy (SLL). Methods:Of 410 women in GOG-0111(a randomized study of cyclophosphamide/cisplatin vs. paclitaxel/cisplatin in stage III and IV ovarian cancer) 139 had available formalin-fixed and paraffin-embedded tumor blocks. Ninety-eight underwent immunocytochemical staining for cyclin D1 and 121 for p57. Cyclin D1 and p57 expression were dichotomized at their medians by percent of positive tumor cells. Fisher’s exact tests were used to compare patient characteristics. PFS and OS for each were compared using Cox proportional hazards models (unadjusted and adjusted for age and stratified by stage, grade, treatment, measurable disease, and histologic cell-type). Response to therapy and proportion with positive SLL were also compared. Results: Of 98 samples stained for cyclin D and 121 samples stained for p57, the median percent positive tumor cell expression was 4.47% for cyclin D (range 0.3-63.2%) and 72.6% for p57 (range 0.6-87.7%). Neither cyclin D1 nor p57 expression were significantly associated with patient characteristics including age, race, performance status, treatment arm, grade, histology, stage or amount of residual disease. In addition, neither was associated with other molecular markers including c-myc, p53, cyclin E, HER2, or p27. In unadjusted and adjusted models for PFS, there was no significant association with percentage of tumor cells positive for cyclin D1 (adjusted HR 1.21, 95% CI 0.73-2.00) or p57 (adjusted HR 0.85, 95% CI 0.54-1.34). OS was similarly not associated with cyclin D1 (adjusted HR 1.12, 95% CI 0.67-1.87) or p57 (adjusted HR 0.75, 95% CI 0.47-1.21) expression. There was also no association of either protein with clinical response (P=0.146 and P=0.433) or positive SLL (P=0.805 and P=0.476). Conclusions: We found no significant association of cyclin D1 or p57 expression with PFS, OS, clinical response or positive SLL. This suggests that cyclin D1 and p57 are not useful prognostic markers in advanced epithelial ovarian cancer.