Título: The Role of HPV and EBV Infection and p53 Gene Mutation in VIN III and Vulvar Cancer
Artigo:
Val ICC1, Almeida GL1, Gondim MC2, Valiante PM2, Takiya CM3, Carvalho MG3.
(1) Gynecology UFRJ, Rio Janeiro, Brazil. (2) Pathology UFRJ, Rio Janeiro, Brazil.
(3) Molecular Biology UFRJ, Rio Janeiro, Brazil.
BACKGROUND: In the last years the human papilloma virus (HPV) has been recognized as a crucial etiological factor for the lower tract genital cancer development, including vulvar cancer. Another oncogenic virus, Epstein-Barr virus (EBV) has been reported to infect the female genital tract. Few studies have addressed the genetic alterations that occur in vulvar squamous carcinomas and their precursor lesions (VIN). Molecular alterations, particularly P53 gene mutation, associated or not to HPV and or EBV infection, that occurs during vulvar carcinogenesis seem to play an important role in vulvar cancer development. The purpose of this study was to clarify the role of human papillomavirus (HPV) and Epstein-Barr virus (EBV) infection in vulvar carcinogenesis in relation to expression of mutated P53 gene.
METHODS: We used PCR to amplify DNA sequences of these viruses and PCR-SSCP analysis to screen for P53 gene mutations in exons 5-8, from formaline-fixed, paraffin embedded blocks including 5 vulvar carcinoma and 8 VIN III specimens.
RESULTS: HPV and EBV DNA were found in 66,7% (4/6) and 0% of VIN III tissues and in 50% (2/4) and 20% (1/5) of vulvar carcinoma specimens, respectively. HPV DNA extraction was not possible in two VIN III and in one vulvar cancer. P53 gene mutation was shown in 25% (2/8) of VIN III lesions and in 25% (1/4) of vulvar carcinoma specimens. P53 analysis was not possible in one vulvar cancer. HPV infection rate was higher in specimens from VIN III specimens as compared with vulvar carcinoma cases. Oncogenic HPV was the predominant type. No correlation was found between P53 gene mutation and/or the presence of viral HPV or EBV DNA. Mutated P53 was almost equally distributed between HPV positive and negative VIN III/ vulvar carcinoma cases.
CONCLUSIONS: Our results suggest that although most of VIN III lesions are associated with HPV infection, P53 mutations may occur independent of viral infection even in the presence of oncogenic HPV.
HPV but not EBV and P53 gene mutation can play a role in the pathogenesis of VIN III and vulvar cancer.