Expression of cell-cycle-associated proteins pRB2/p130 and p27(kip1) in vulvar squamous cell carcinomas

Squamous cell vulvar carcinoma accounts for 4% of all gynecologic malignanc ies. The cause of vulvar cancer is still unclear. Identification of new bio logic factors involved in vulvar carcinogenesis may be useful in clarifying the natural history of this malignancy. We investigated the immunohistoche mical expression of the retinoblastoma-related proteins pRB2/p130 and CKI p 27(kip1) in a series of 51 invasive squamous cell carcinomas of the vulva ( ISCCs) and in synchronous normal vulvar skin, non-neoplastic epithelial dis orders (NNED) and vulvar intraepithelial neoplasia (VIN). Normal vulvar ski n staining showed positivity for both pRB2/p130 and p27(kip1) 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/p1 30 expression from NNED to neoplastic tissues (VIN and ISCCs) (P =.004). Lo ss of p27(kip1) expression was found in 16 of 51 specimens (31%) of invasiv e carcinomas, in 1 (14%) of 7 specimens of VIN, and in 2 of 18 specimens of NNED (11%). pRR2/p130 and p27(kip1) did not correlate significantly with a ny of the clinicopathologic parameters examined. Our data indicate that los s of pRB2/p130 and p27(kip1),are frequent events in invasive vulvar carcino mas compared with synchronous premalignant lesions, nonneoplastic epithelia l disorders, and normal vulvar skin. The significant progressive decrease o f pRB2/p130 expression from non-neoplastic epithelial alterations through i ntraepithelial neoplasia to invasive vulvar carcinomas suggests a role for this tumor suppressor gene in vulvar carcinogenesis. Copyright (C) 2001 by W.B. Saunders Company