Nuclear P27 expression in benign, borderline (LMP) and invasive tumors of the ovary and its association with prognosis: A gynecologic oncology group study

Objective: Nuclear p27 expression was examined in non-invasive and invasive ovarian tumors from a cross-sectional study, and clinical relevance of p27 was evaluated in the primary tumors from women participating in two randomized phase III treatment trials. Methods: An immunohistochemistry assay was used to detect p27 in formalin-fixed paraffin-embedded ovarian tumors from 3 distinct sources. Results: Among the initial 91 ovarian tumors tested, low p27 expression (< 50% positive cells) was observed in 5.4% of non-invasive tumors versus 42.6% of invasive tumors (p < 0.001). In 145 ovarian cancers with high-risk early stage disease, 16.5% exhibited low p27 expression, and categorized p27 was not associated with age, race, or performance status. Low expression of p27 was common in poorly differentiated tumors (35.7%) compared to moderately (15.0%) and well (9.5%) differentiated tumors (p = 0.024) and rare in clear cell carcinomas (2.4%) compared to other histologies (p = 0.014). In the 139 cancers with advanced disease, 60% displayed low p27 expression, and categorized p27 expression was not associated with age, race, performance status, tumor grade, histologic subtype, measurable disease status or survival. Exploratory analyses revealed an association of cyclin E to p27 ratio > 1.0 with an increased risk of death (hazard ratio = 1.53; p = 0.017). Conclusions: Low p27 expression could be associated with malignant transformation of the ovarian epithelium and FIGO stage. A cyclin E to p27 ratio > 1.0 may be associated with shorter survival in these patients. Further study is required to confirm the trend for increased recurrences with low p27 expression in early stage disease.