Intraepithelial Neoplasia and HPV Status in Penile Intraepithelial Lesions
Mark J Mentrikoski, Stephen Culp, Helen P Cathro, Henry F Frierson, Edward B Stelow. University of Virginia, Charlottesville, VA
Background: Recently, precursors of invasive penile carcinomas termed penile intraepithelial lesions (IELs), have been shown to consist of two morphologic variants: the non-HPV-related differentiated type and the HPV-related undifferentiated type. They remain incompletely studied due to the low incidence of disease in the developing world. We therefore examined the HPV status and expression of several immunohistochemical markers in IELs in a cohort of American patients with penile carcinomas.
Design: 61 cases of penile squamous cell carcinoma from 57 patients were retrieved from the archives. Within these, IELs were identified in 56 cases. IEL was categorized into differentiated, undifferentiated, or mixed types. Histologic classification of associated primary tumor variants was also examined. Immunohistochemical stains for p16, p53, EGFR, and cyclin D1, as well as chromogenic in situ hybridization for high-risk HPV and Her2/neu were performed in all cases.
Results: IELs consisted of 33 differentiated (59%), 16 undifferentiated (29%), and 7 mixed (12%) variants. Differentiated IELs were strongly associated with the usual histologic variant (30/33) of invasive carcinoma, while undifferentiated IELs occurred most commonly adjacent to basaloid (4/4) and warty (6/6) variants. p16 was overexpressed in nearly all undifferentiated cases (94%, p=<0.001) and in the majority of mixed (71%) variants. p16 was detected in 24% of differentiated IELs, but the staining was not diffuse and generally weak. The highest rate of high-risk HPV detection occurred in p16 positive, undifferentiated IELs (9/15, p=<0.001); it occurred in only one differentiated IEL, and this case had diffuse p16 staining. p53, EGFR, and cyclin D1 overexpression was detected more frequently in differentiated IELs, occurring in 45%, 88%, and 85%, respectively, compared to 12%, 50% and 75%, respectively, for undifferentiated IELs. p53-positivity was inversely correlated with p16-positivity (p=0.001). Her2/neu was not amplified in any case.
Conclusions: Similar to premalignant lesions of the vulva, most penile IELs can be easily classified into differentiated and undifferentiated variants. The latter is more closely associated with p16 positivity and HPV infection. The differentiated variant is more often found to overexpress p53, EGFR, and cyclin D1. Both are associated with specific variants of invasive squamous cell carcinoma.
Category: Genitourinary (including renal tumors)
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 143, Monday Morning