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.


METHODS
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.


CONCLUSIONS
P16 is a putative molecular biomarker of cervical adenocarcinoma. Overexpression appears to primarily reflect HPV-induced cell cycle dysregulation.
Schorge
John O
JO
Laboratory of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Tex, USA. john.schorge@utsouthwestern.edu
Lea
Jayanthi S
JS
Elias
Keren J
KJ
Rajanbabu
Ramababu
R
Coleman
Robert L
RL
Miller
David S
DS
Ashfaq
Raheela
R
D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology / Q000821:virology; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D027383:Papillomaviridae / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D002583:Uterine Cervical Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000821:virology
D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral