Prognostic Significance of Aurora-A and BRCA2 Expression in Endometrioid Ovarian Carcinoma.
Fan Yang, Xiaoqing Guo, Gong Yang, Daniel G Rosen, Jinsong Liu. The University of Texas MD Anderson Cancer Center, Houston
Background: Aurora-A, a serine/threonine kinase, has been shown to regulate the cell cycle checkpoint and maintain genomic integrity. Aurora-A is overexpressed in various carcinomas. Breast cancer susceptibility gene 2 (BRCA2) plays an important role in maintaining genomic stability and acts as a tumor suppressor. Our recent study suggested that Aurora-A regulates genomic instability and tumorigenesis through cell cycle dysregulation and suppression of BRCA2 expression. However, the expression of Aurora-A, BRCA2 and their clinical significance is unknown in endometrioid ovarian cancer.
Design: In this study, we determined Aurora-A and BRCA2 expression in endometrioid ovarian carcinoma and correlated them with clinicopathologic characteristics and patient survival. Immunohistochemical staining was performed in 51 primary endometrioid ovarian carcinoma tumor samples using tissue microarray. We then analyzed the associations between Aurora-A and BRCA2 expression and clinical factors (tumor grade, disease stage, surgical type, clinical response, and relapse) and overall and disease-free survival durations.
Results: Aurora-A and BRCA2 expression were found in 48% and 29% of samples, respectively. The results of Fisher's exact test suggested that Aurora-A expression was significantly associated with no family history of ovarian cancer (P=0.03) and that BRCA2 expression was associated with early-stage disease (P=0.03), low ascites incidence (P=0.03), younger age (<60) at diagnosis (P=0.03), and low-grade tumors (P<0.01). The nuclear BRCA2 score was negatively correlated with Aurora-A score (P=0.019, two-tailed Pearson correlation). A log-rank test demonstrated that Aurora-A expression was associated with shorter overall (P=0.001) and disease-free (P=0.009) survival durations and that BRCA2 expression was associated with longer overall (P=0.000) and disease-free (P=0.002) durations. Patients with BRCA2-positive and Aurora-A-negative tumors had higher overall (P=0.001) and disease-free (P=0.001) survival rates than did patients with Aurora-A-positive and BRCA2-negative tumors.
Conclusions: Our results demonstrate that a negative regualory loop exists between Aurora-A and BRCA2 expression in ovarian endometrioid carcinoma. Aurora-A expression is an unfavorable prognostic factor in patients with endometrioid ovarian cancer and BRCA2 is favorable, combination of these two markers may better predict the prognosis of patients with endometrioid ovarian carcinoma than individual marker alone.
Category: Gynecologic & Obstetrics
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 109, Tuesday Afternoon