Overexpression of ANXA1 in penile carcinomas positive for high-risk HPVs

Abstract

The incidence of penile cancer varies between populations but is rare in developed nations. Penile cancer is associated with a number of established risk factors and associated diseases including phimosis with chronic inflammation, human papillomavirus (HPV) infection, poor hygiene and smoking. The objective of this study was to identify genes related to this type of cancer. The detection of HPV was analyzed in 47 penile squamous cell carcinoma samples. HPV DNA was detected in 48.9% of penile squamous cell carcinoma cases. High-risk HPV were present in 42.5% of cases and low-risk HPV were detected in 10.6% of penile squamous cell carcinomas. The RaSH approach identified differential expression of Annexin A1 (ANXA1), p16, RPL6, PBEF1 and KIAA1033 in high-risk HPV positive penile carcinoma; ANXA1 and p16 were overexpressed in penile squamous cells positive for high-risk HPVs compared to normal penile samples by qPCR. ANXA1 and p16 proteins were significantly more expressed in the cells from high-risk HPV-positive penile carcinoma as compared to HPV-negative tumors (p<0.0001) independently of the subtype of the carcinoma. Overexpression of ANXA1 might be mediated by HPV E6 in penile squamous cell carcinoma of patients with high-risk HPVs, suggesting that this gene plays an important role in penile cancer.

Figure 1. Relative expression media of the selected genes for validation using qPCR.

Figure 2. Immunolocalization of annexin A1 (ANXA1) and p16 in human primary penile squamous cell carcinoma and histologically normal tumor margins.

ANXA1 immunostaining in A) Histologically normal tumor margins; B) Human primary penile squamous cell carcinoma HPV-negative; C) Human primary penile squamous cell carcinoma positive for high-risk HPV. p16 immunostaining in D) Histologically normal tumor margins; E) Human primary penile squamous cell carcinoma HPV-negative; F) Human primary penile squamous cell carcinoma positive for high-risk HPV. G) Reaction control for ANXA1. H) Graphic of densitometry of the immunostaining of ANXA1 in the samples analyzed. I) Graphic of densitometry of the immunoistaining of p16 in the samples analyzed. Bars = 50 µm. (** = p<0.01; **** = p<0.0001; &&&& = p<0.0001, Tukey’s post hoc test).