NOTCH2 expression is decreased in epithelial ovarian cancer and is related to the tumor histological subtype

Abstract

Notch family members function as both oncogenes and tumor suppressors. NOTCH2 is down-regulated in colon cancer, and reduced expression is associated with a less differentiated, more aggressive phenotype, and reduced overall survival. NOTCH2 has also been shown to have pro-apoptotic and growth suppressive effects in thyroid carcinoma, and carcinoid tumors. The expression pattern of NOTCH2 in ovarian cancer is unknown. An immunohistochemical analysis using a polyclonal antibody to the NOTCH2 intracellular domain was performed on a total of 119 ovarian carcinomas, and 7 serous borderline tumors, arranged onto tissue arrays. Normal ovarian and fallopian tube epithelium were used as controls. Specimens were scored as low or high NOTCH2 expression. The score distributions for the subtypes were analyzed with the chi square test. Fifty two of 61 (85.2%) papillary serous, eight of 13 (61.5%) clear cell, and 23 of 30 (76.7%) endometrioid, demonstrated negative or lower NOTCH2 expression than normal fallopian tubal epithelium or ovarian surface epithelium. In contrast, 10 of 15 (66.7%) mucinous carcinomas had a high level of NOTCH2 expression and consistently demonstrated intense polarized staining (P<.001). The apical expression of NOTCH2 protein present in the normal fallopian tube epithelium and many borderline tumors was absent in the high grade carcinomas, most notably in papillary serous. Decreased NOTCH2 expression is associated with the poorly differentiated serous epithelial ovarian carcinoma histology. Further studies are needed to assess the functional role of NOTCH2 in ovarian cancer and its effect on prognosis.