Detection of Human Papillomavirus DNA, P53 and KI67 Expression in Penile Carcinomas

Abstract

Our study is aimed at evaluating the presence of p53 and Ki67 expression by immunohistochemistry in a series of 11 paraffin-embedded penile carcinomas. We also investigated the presence of Human Papillomavirus (HPV) DNA in these tumours and performed an accurate typing by DNA sequencing on positive samples. Immunohistochemistry (IHC) was performed with the anti-p53 and Ki67 mouse monoclonal antibodies. DNA extracted from small sections of each specimen was submitted to amplification with HPV specific general primers; PCR products ofthe proper length were purified and sequenced. IHC demonstrated nuclear accumulation of mutated p53 and Ki 67 expression in 10/11 tumour samples (90.9%). The prevalence of HPV DNA was 72.7%; the most prevalent type was HPV16. Sequencing analysis revealed the presence of HPV53 (12.5%), HPV18 (25%) and HPV16 (62.5%). Out of the p53 or Ki67 positive carcinomas the percentage ofHPV positives was 80% and 70% respectively. Our results indicate that penile carcinoma is frequently associated to high risk HPV and with diffuse p53 and Ki67 expression.Invasive cancer of the penis is a relatively uncommon disease in Western countries (0.I-0.9 per 100,000 males in Europe and0.7-0.9 per 100,000 males in the USA) whereas the highest incidence occurs in developing countries; in someareasofAsia, Africa and South America the incidence of penile carcinoma is significantly higher, reaching 19per 100,000 males. In these countries, penile carcinoma accounts for as much as 10-20% of male cancer(I). This carcinoma spreads locally to regional lymph nodes which are often surgically treated. This procedure has a high morbidity rate(30-90%) (2); thusthe majorissue in treating penile cancer involves the decision of which patient should or should not be submitted to lymph node. dissection. Many groups have identified prognostic factors for the incidence of lymph node metastases to avoid surgical morbidity such as: tumour thickness, histopathological grade, and venous and lymphatic embolization by neoplastic cells (3).In recent years human Papillomaviruses (HPVs) have been identified as possible etiological agents for the disease but thecorrelationbetweenthe viral DNA presence and the prognosis is stilluncertain (4 human papillomavirus (HPV) in cervical carcinomas and the association between HPV and cervical cancer has now been ascertained to reach 99.7% (5). The overall frequency of HPV DNA detection in carcinoma of the penis is far lower, nonetheless the reported prevalence of HPV is highly variable, from 15% to 70%, depending on the sensitivity of the detection method and on the tumour type (6-8). Moreover, only a few studies have analyzed penile carcinogenesis considering both the HPV status and the histological differentiation.The progress in molecular biology techniques makes it possible to analyse several neoplastic diseases by the identification of oncogene activation and/or tumour suppressor gene inactivation. The tumour suppressor gene p53 is located in the short arm of chromosome 17 and has been implicat...

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