P16 As a Molecular Biomarker of Cervical Adenocarcinoma

Objective: Cervical adenocarcinomas are increasing in incidence each year. The aim of this study was to identify a molecular biomarker to improve early detection.

Study Design: Fifty-five in situ and invasive cervical adenocarcinomas were compared with 5 normal endocervical controls by immunohistochemical analysis of p16, p21, p27, cyclin D1, cyclin E, p53, and Ki-67. Expression was scored from 0 to 8 by using an automated imaging system. Western blotting and polymerase chain reaction-based human papillomavirus (HPV) testing were performed on 16 of the invasive cases having fresh-frozen tissue.

Results: P16 exhibited a higher mean expression score for in situ (7.4; P<.0001) and invasive cervical adenocarcinoma (6.6; P<.0001) versus controls (2.0). A cutoff p16 expression score of 5 had a sensitivity of 94.5% and a specificity of 100%. Western blotting confirmed p16 protein expression. Fourteen (88%) of 16 invasive cervical adenocarcinomas were HPV-positive.

Conclusion: P16 is a putative molecular biomarker of cervical adenocarcinoma. Overexpression appears to primarily reflect HPV-induced cell cycle dysregulation.