AURKA and BRCA2 expression highly correlate with prognosis of endometrioid ovarian carcinoma

Abstract

Aurora kinase A (AURKA), a serine/threonine kinase, has been shown to regulate the cell cycle checkpoint and maintain genomic integrity. AURKA is overexpressed in various carcinomas. Breast cancer 2, early onset (BRCA2) has an important role in maintaining genomic stability and acts as a tumor suppressor. Our recent study suggested that AURKA regulates genomic instability and tumorigenesis through cell cycle dysregulation and suppression of BRCA2 expression. However, the expression of AURKA, BRCA2 and their clinical significance is unknown in endometrioid ovarian cancer. In this study, we determined AURKA 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 AURKA and BRCA2 expression and clinical factors (tumor grade, disease stage, surgical type, clinical response, and relapse) and overall and disease-free survival durations. AURKA and BRCA2 expression were found in 48 and 29% of the samples, respectively. The results of Fisher's exact test suggested that AURKA 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 AURKA score (P=0.019, two-tailed Pearson correlation). A log-rank test demonstrated that AURKA 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 AURKA-negative tumors had higher overall (P=0.001) and disease-free (P=0.001) survival rates than did patients with AURKA-positive and BRCA2-negative tumors. Our results demonstrate that a negative regulatory loop exists between AURKA and BRCA2 expression in the ovarian endometrioid carcinoma. AURKA 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.

Figure 1

BRCA2 and AURKA expression in endometrioid ovarian carcinoma. (a) Endometrioid ovarian carcinoma cells show nuclear staining for BRCA2 (×400). (b) AURKA-negative staining in endometrioid ovarian carcinoma (×400). (c) BRCA2-negative staining in endometrioid ovarian carcinoma (×400). (d) Diffuse positive staining for AURKA in endometrioid ovarian carcinoma (×400).

Figure 2

Kaplan–Meier estimates for (a) AURKA disease-free survival, (b) AURKA overall survival, (c) BRCA2 disease-free survival, (d) BRCA2 overall survival, (e) AURKA and BRCA2 disease-free survival, and (f) AURKA and BRCA2 overall survival.