Immunohistochemical staining for p16INK4A selectively detects human papillomavirus-related premalignant and malignant vulvar lesions

Abstract

5028 Background: Two distinct types of vulvar carcinomas have been delineated which differ in terms of clinical presentation and outcome. The first, usually of basaloid or warty type is frequently preceded by the undifferentiated form of vulvar intraepithelial neoplasia (VIN) and is human papillomavirus (HPV)-related. The second, generally keratinizing, is frequently associated with the differentiated form of VIN as well as with lichen sclerosus and squamous cell hyperplasia and arises through HPV non-related pathways. p16 overexpression secondary to inhibition of pRb induced by the action of the E7 viral oncoprotein has been described in HPV-related tumors and premalignant lesions in different settings. However, p16 overexpression has not been analyzed in vulvar lesions. The aim of this study is to determine p16 immunohistochemical expression in a large serie of vulvar carcinomas and their precursors including HPV and non-HPV related histologies. Methods: Tissue samples from 120 cases with epithelial neoplastic, hyperplastic and normal lesions of the vulva were included in this study. The samples were fixed in 10% formalin and paraffin embedded. Immunohistochemical studies were done using a p16 antibody (p16INK4A Research Kit, Dako) in the automated immunohistochemical system TechMate 500 using the EnVision method (Dako Co, Carpinteria, CA, USA). Results: p16 was strongly positive in all HPV-related histologies: basaloid/condilomatous VIN (30/30), basaloid (7/7) and warty (2/2) carcinomas, and in a small proportion of seborrheic keratosis and condiloma acuminata (14 and 22% respectively). In contrast, p16 was consistently negative in HPV-unrelated lesions: normal skin (0/41), squamous cell hyperplasia (0/20), lichen sclerosus (0/19), differentiated VIN 3 (0/11), keratinizing squamous cell carcinoma (0/30), and verrucous carcinoma (0/2). Conclusions: p16 immunostaining is a good discriminator between HPV-related and HPV-unrelated vulvar carcinomas and VINs. No significant financial relationships to disclose.