p16 as a Molecular Biomarker of Cervical Adenocarcinoma
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Am J Obst Gynecol 2004; 190:668
John O. Schorge, Jayanthi S. Lea, Keren J. Elias, Ramababu Rajanbabu, Robert L. Coleman, David S. Miller, Raheela Ashfaq
Cervical adenocarcinomas are increasing in incidence each year. The aim of this study was to identify a molecular biomarker to improve early detection.
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.
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.
P16 is a putative molecular biomarker of cervical adenocarcinoma. Overexpression appears to primarily reflect HPV-induced cell cycle dysregulation.