HPV Infection and Correlation with the Expression of Cell Cycle Markers in Verrucous Carcinoma of the Penis
DM Berney, E Stankiewicz, S Kudahetti, X Zhang, N Watkin, E Ktori, D Prowse, C Corbishley. Barts and The London Medical School, London, United Kingdom; St George's Hospital, London, United Kingdom
Background: Penile verrucous carcinoma and verruciform tumours are rare and little is known of their aetiology or pathogenesis. We wished to correlate the expression of cell cycle markers with human papilloma virus (HPV) typing in verruciform carcinomas to understand possible mechanisms of their pathogenesis.
Design: In this study we examined cell cycle protein expression in a uniquely large series of penile verrucous carcinomas and their correlation with HPV infection, in comparison with usual type squamous cell carcinomas of the penis. The expression of the cell cycle associated proteins p53, p21, Rb, p16 and Ki-67 were examined by immunohistochemistry in 15 pure verrucous carcinomas, 4 verruciform carcinomas with warty features and four mixed squamous/verrucous tumours. HPV detection was performed by PCR to allow subtyping of the virus detected. Results were compared with a set of usual type squamous cell carcinomas (n=103). Samples were tested on tissue micro-array sections, and scored in a semi-quantitative manner.
Results: Of 23 verruciform tumours, p53 expression was present in 68% of cases often with a basaloid distribution pattern, p21 in 62% and p16 in 9% of patients. Rb was expressed in 83% of the tumours. The expression of p16 was significantly lower in verruciform carcinomas than in keratinizing SCC (p=0.0008). Ki67 also showed significantly lower expression in VC cases (p=0.0007) and also was predominantly basaloid in distribution. Of thirteen out of fifteen pure verrucous tumours analysed by PCR, only 3 showed HPV infection, and none for the high risk HPV types 16 or 18. Of 3 warty verruciform tumours assessed, all showed HPV infection, two showing HPV16 infection.
Conclusions: Pure penile verrucous carcinoma pathogenesis is in all probability unrelated to any HPV subtype, and this is reflected in the low p16 immunochemistry. The low Ki-67 index reflects their slow growing nature. P53 and Ki-67 expression show a different pattern with basal and supra-basal staining. However p21 and Rb immunochemistry are less useful in differentiation from keratinizing SCCs. It is uncertain whether the high expression of p53 seen is due to gene mutation or overexpression of the wild type protein, however the distribution pattern suggests the latter.
Category: Genitourinary (including renal tumors)
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 119, Tuesday Afternoon