Expression of HPV L1 Capsid Protein in Anal Condyloma and Anal Squamous Intraepithelial Neoplasia (ASIN)
Deepa T Patil, Bin Yang. Cleveland Clinic, Cleveland, OH
Background: Morphologic evaluation and grading of anal dysplasia on biopsies remains problematic, especially in cases with limited sample. Although a handful of studies have evaluated the role of p16 as a surrogate biomarker in the diagnosis of anal squamous dysplasia, the expression of HPV L1, a capsid protein that confers viral entry ability, has never been analyzed in this regard. The aim of our study is 1) to systematically study the expression of HPV L1 capsid protein in anal condyloma and anal squamous dysplasia and 2) to correlate HPV L1 expression with p16 expression and grade of dysplasia (low grade/high-grade ASIN).
Design: A total of 80 anal lesions were retrieved and histologically reviewed. Expression of nuclear HPV L1 was studied using combined immunohistochemistry and in situ hybridization technique from Advanced Medical Science. p16 immunohistochemistry was performed with antibody from Ventana (clone E6H4). Two p16 immunostaining patterns were recorded: diffuse and full thickness staining and patchy/focal staining. HPV L1 and p16 expression was correlated with grade of dysplasia using Chi2 analysis.
Results: Eighty anal lesions included 11 condyloma, 39 low-grade ASIN (AIN1) and 30 high-grade ASIN (AIN2-3). Expression of HPV L1 was seen in 31.3% (25/80) of all anal lesions, including 64% (7/11) condylomas, 46% (18/39) low-grade ASIN and 0% of high-grade ASIN lesions. The difference of HPV L1 expression between low-grade and high-grade ASIN lesions was statistically significant (p<0.001). p16 expression was identified in 86.3% (69/80) of all anal lesions. Of these, 38 lesions showed patchy staining pattern and 31 had diffuse staining pattern. Patchy p16 staining pattern was observed in 64% of condylomas and 80% of low-grade ASIN lesions, but not in high-grade ASIN lesions. In contrast, diffuse p16 staining pattern was found in 100% (30/30) of high-grade ASIN and only in 2.6% (1/39) of low-grade ASIN lesions. The difference of p16 patterns between low grade and high grade ASIN was statistically significant (p<0.001).
Conclusions: HPV L1 capsid protein is mainly expressed in anal condylomas and low-grade ASIN lesions and its expression is lost in high-grade ASIN. The two patterns of p16 immunostaining may have different biologic implications. Patchy p16 staining pattern is a feature of low-grade ASIN and some anal condylomas, while diffuse p16 staining pattern is a hallmark of high-grade ASIN. Our study indicates that application of p16 and HPV L1 immunohistochemistry can facilitate the accurate diagnosis and grading of anal squamous dysplasia.
Tuesday, March 20, 2012 9:00 AM
Platform Session: Section D, Tuesday Morning