β-catenin nuclear localization is associated with grade in ovarian serous carcinoma

Abstract

Objectives β-Catenin has been previously associated with oncogenic activity in human cancers. We evaluated whether β-catenin also plays a role in papillary serous ovarian neoplasms. Methods Immunohistochemistry for β-catenin was performed on the primary ovarian serous neoplasms of 105 women. Of these, 10 were low malignant potential (LMP) serous tumors, and 95 were serous cancers. Nuclear β-catenin staining was correlated with grade of tumor and median survival. OVCAR-3, OVCA-420, OVCA-432, and MDAH-277-10c were evaluated for β-catenin localization and transfected with a T-cell factor (TCF) responsive reporter to evaluate β-catenin transcriptional activity. Results Of 105 serous tumors, 13 (12.3%) demonstrated β-catenin nuclear staining. Eleven of 48 high-grade serous carcinomas (23.0%) demonstrated nuclear staining compared with 1 low-grade serous carcinoma (2.1%) ( P = 0.006). One LMP tumor had nuclear staining. β-Catenin nuclear localization was undetectable in the cell lines tested. Furthermore, transient transfection of the cell lines with a TCF-responsive reporter did not demonstrate significant constitutive transcriptional activation. Conclusions We found a statistically significant correlation between β-catenin nuclear localization and ovarian high-grade serous carcinomas. Thus, deregulation of β-catenin may play a role in the pathogenesis of ovarian high-grade serous carcinomas in contrast to ovarian low-grade serous carcinomas and LMP serous tumors.