[1270] Co-Expression Patterns of HPV L1 and p16 in Anal Squamous Intraepithelial Neoplasia

Bin Yang, Deepa Patil. Cleveland Clinic, Cleveland, OH

Background: HPV L1 produces capsid protein to protect the viral genome and confer contagiosity. It is mainly expressed in the episomal stage and its expression is suppressed after HPV integrated in host genome. HPV L1 expression is inversely correlated with the expression of E6 and E7 oncoproteins. Elevation of E7 and subsequent degradation of pRb in turn triggers p16 overexpression. AIN is a precursor of the anal squamous carcinoma linked to HPV infection. Histopathologically, it is often challenging to accurately grade AIN. To investigate the role of HPV L1 and p16 in anal dysplasia, we studied the immunohistochemical co-expression patterns of HPV L1 and p16 in anal condyloma, AIN1 and AIN2-3 lesions.
Design: Anal biopsies with condyloma and AIN were retrieved and histologically reviewed. Expression of nuclear HPV L1 was studied using combined immunohistochemistry and in situ hybridization technique from Advanced Medical. p16 immunohistochemistry was performed using Ventana antibody. Only diffuse, full-thickness nuclear and cytoplasmic p16 staining was considered as positive. Patch p16 cstaining was excluded in this study.
Results: Co-expression of HPV L1 and p16 was analyzed in 53 anal lesions, including 10 condylomas, 21 AIN1 and 22 AIN2-3. There were 18 cases immunoreactive to HPV L1 and 23 cases showing p16 positivity. The immunostaining patterns of both HPV L1 and p16 are tabulated below.

HPV L1p16CondylomaAIN 1AIN 2-3

Briefly, expression of HPV L1 and p16 diffuse staining pattern was mutually exclusive in all the cases except one, which showed focal high grade AIN2 in a background of extensive AIN1. Expression of HPV L1 but lack of p16 expression was seen in 70% condyloma and 47.6% of AIN1, but none of AIN2-3 lesions. In contrast, diffuse p16 expression with lack of HPV L1 staining was seen in all high grade AIN and only in 4.7% (1/21) of AIN2-3. None of the condyloma cases showed diffuse p16 staining. Lack of both HPV L1 and p16 expression was seen in 30% of condyloma and 47.6% of AIN1.
Conclusions: Our study indicates that the expression of HPV L1 and p16 is mutually exclusive in a majority of anal condyloma and AIN. Expression of HPV L1 represents a biological episomal stage and usually seen in low grade lesions and diffuse p16 expression represents an integrated stage of malignant transformation. Our data suggests that application of both HPV L1 and p16 biomarkers can not only facilitate accurate grading of AIN, but also add risk assessment value of the anal lesion.
Category: Gynecologic & Obstetrics

Wednesday, March 21, 2012 1:00 PM

Poster Session VI # 181, Wednesday Afternoon


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