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Maria Geruza Marques Fernandes, Francisco Valdeci Almeida Ferreira, Selma Nogueira Holanda Ferreira, Sônia Maria Sucupira Lima, Francisco Dário Rocha Filho, Ana Virgínia MF Ribeiro, Sílvia H Rabenhorst, Susana M Mesquita, Glauber Ferreira e Luiza HM Amorim

Abstract

The aim of this investigation was to study the cell proliferation index (MIB-1) and p53 expression in 24 invasive squamous cell lesions (ISL, CEC), 7 high-grade squamous cell intraepithelial lesions (HSIL) and 11 low-grade intraepithelial lesions(LSIL) of the penis; and correlate them with age, HPV occurrence and the histopathological features. In addition, HPV status was detected by in situ hybridization (ISH) in 20 invasive lesions. MIB1 and p53 expressions were evaluated by percentiles and scores (1 to 9, according dispersion of marked nuclei plus reaction intensity) Results: the mean age of occurrence was 62.3 yrs for the ISL; 41.6 yrs for HSIL and 33.2 yrs in the case of LSIL. The MIB-1 showed its highest expression in HSIL (46.1%), followed by the ISL (34.5%), and the LSIL (13.3%). p53 over-expression was mainly seen in 90.9% of LSIL; in 70.9% of ISL and in 57.1% of HSIL The cytohistopathological signals for HPV were seen in 72.7% of low grade lesions, in 87% of the invasive lesion and 100% of the severe dysplasia. The HPV-DNA was detected in 30% of the ISL. In conclusion, MIB-1 and p53 showed to be independent markers and were straight related to the progression and severity of these lesions. The p53 scores increased from the low to the high grade and invasive lesions and probably suggests an early inhibition by HPV proteins, mutations coming up later. There is a clear age-related prevalence of lesions, similar to the vulvar and cervical HPV related-lesions’ evolution, but penile carcinoma is delayed.

Key words: squamous cell carcinoma; penile neoplasms; human papillomavirus; in situ hybridization; p53; MIB-1.