Clinical Value of p16 Biomarker in Low Grade Squamous Intraepithelial Lesions
Nicole A Pele, Mary M Tomic, Eric C Huang. University of California, Davis Medical Center, Sacramento, CA
Background: The biomarker p16 has been investigated extensively for utility in squamous intraepithelial lesions. However, studies on the clinical value and appropriateness of p16 immunohistochemistry (IHC) in low grade squamous intraepithelial lesion (LSIL) are limited and remain unclear. Recently, the Lower Anogenital Squamous Terminology (LAST) Project issued limited recommendations on the use of p16 IHC as biomarker in human papilloma virus (HPV)-associated lesions. The objective of this study is to evaluate the utility of p16 as a potential biomarker in predicting the clinical risk behavior in LSIL cervical biopsies.
Design: An institutional retrospective review of all cervical biopsies from 2008-2010 by Pathology Laboratory Information System identified 66 cases with a histologic diagnosis of LSIL. Of these, 37 (56%) cases with greater than one year follow-up data (pap smears, high-risk HPV status, biopsies and excisions) were included in the study. Upon re-review by a gynecologic pathologist, 20 confirmed LSIL cases were stained for p16 IHC using the EnVision+ system (Dako Cytomation, Glostrup, Denmark). Positive p16 staining was defined as strong diffuse staining in at least the basal 1/3 of the epithelium. Staining patterns and clinical follow-up outcome were analyzed.
Results: In all 20 LSIL cases, HPV+ was detected in 65% (n=13), p16+ was identified in 50% (n=10), and HPV+ p16+ was seen in 35% (n=7) of cases. For the p16+ LSILs, clinical regression and persistence occurred in 90% (n=9) and 10% (n=1) of cases, respectively. In LSILs that are HPV+ p16+, 86% (n=6) regressed while 14% (n=1) persisted. In addition, HPV+ p16- LSILs showed 67% (n=4) regression, 17% (n=1) persistence, and 17% (n=1) progression. Interestingly, p16 was negative in two LSILs with clinical follow-up of cervical intraepithelial neoplasia (CIN) 2 and 3.
Conclusions: This study demonstrates that p16 IHC is a poor predictor of clinical outcome and supports the LAST recommendation against the use of p16 IHC in morphologic LSILs. In addition, our data show that half of LSILs have strong diffuse positive staining for p16. As LAST recommends the usage of p16 IHC when entertaining the interpretation of CIN2, the possibility of over-interpreting LSIL with strong diffuse positive p16 as CIN2 may lead to subsequent over-treatment of lesions that are likely to regress.
Category: Gynecologic & Obstetrics
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 225, Tuesday Afternoon