Expression of cell-cycle-associated proteins pRB2/p130 and p27kip in vulvar squamous cell carcinomas.

Squamous cell vulvar carcinoma accounts for 4% of all gynecologic malignancies. The cause of vulvar cancer is still unclear. Identification of new biologic factors involved in vulvar carcinogenesis may be useful in clarifying the natural history of this malignancy. We investigated the immunohistochemical expression of the retinoblastoma-related proteins pRB2/p130 and CKI p27kip1 in a series of 51 invasive squamous cell carcinomas of the vulva (ISCCs) and in synchronous normal vulvar skin, non-neoplastic epithelial disorders (NNED) and vulvar intraepithelial neoplasia (VIN). Normal vulvar skin staining showed positivity for both pRB2/p130 and p27kip1. Loss of pRB2/p130 occurred in 29 (57%) of 51 specimens of ISCCs, and in 1 of 7 specimens with VIN (14%; P = .04). We also observed a significant decrease of pRB2/p130 expression from NNED to neoplastic tissues (VIN and ISCCs) (P = .004). Loss of p27kip1 expression was found in 16 of 51 specimens (31%) of invasive carcinomas, in 1 (14%) of 7 specimens of VIN, and in 2 of 18 specimens of NNED (11%). pRB2/p130 and p27(kip1) did not correlate significantly with any of the clinicopathologic parameters examined. Our data indicate that loss of pRB2/p130 and p27kip1 are frequent events in invasive vulvar carcinomas compared with synchronous premalignant lesions, non-neoplastic epithelial disorders, and normal vulvar skin. The significant progressive decrease of pRB2/p130 expression from non-neoplastic epithelial alterations through intraepithelial neoplasia to invasive vulvar carcinomas suggests a role for this tumor suppressor gene in vulvar carcinogenesis.