P16INK4A overexpression and HPV infection in uterine cervix adenocarcinoma

Abstract

Human papillomaviruses (HPVs) are causally involved in the genesis of cervical carcinomas and their precursors, and there is a strong relationship between the cyclin-dependant kinase inhibitor p16INK4A and HPV infection. This study was carried out to assess the correlations between p16INK4A expression as an early biomarker of the endocervical adenocarcinoma and HPV infection. p16INK4A expression and HPV typing were performed on 46 samples including 5 normal endocervix, 9 benign lesions of the endocervix, 25 endocervical adenocarcinomas, and 7 endometrioid adenocarcinomas of the uterine corpus. A semiquantification of the p16INK4A immunostaining was realized (using both the staining intensity and the percentage of positive cells) and was graded from 0 to 15. All of the 25 endocervical adenocarcinomas overexpressed p16INK4A; the adjacent epithelium and the connective tissue were strictly negative. No p16INK4A was detected in nine benign endocervical lesions and in five normal endocervix. Few endometrioid adenocarcinomas of the uterine corpus that infiltrate the endocervix exhibited a low immunoreactivity (score 0/15 or 1/15). This pattern of expression is significantly associated with HPV infection (p<10(-3)), mainly high-risk HPV types (p=0.02). Our results suggest that p16INK4A is a putative molecular biomarker that consistently discriminates uterine cervix adenocarcinomas from benign lesions and from endometrioid adenocarcinomas of the uterine corpus.