Ha-ras oncogene mutation associated to progression of papillomavirus induced lesions of uterine cervix

• Published in: Journal of clinical virology 2003-08, Vol.27 (3), p.263-269
• Main Authors: Alonio, Lidia Virginia, Picconi, Maria Alejandra, Dalbert, Delia, Mural, Juan, Bartt, Ofelia, Bazán, Graciela, Dominguez, Mariana, Teyssié, Angélica Rita
• Format: Article
• Language: English
• Subjects: Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - virology; Cervical cancer; Cervical Intraepithelial Neoplasia - pathology; Cervical Intraepithelial Neoplasia - virology; Cervix Uteri - pathology; Cervix Uteri - virology; Disease Progression; Female; Genes, ras - genetics; Ha-ras mutations; HPV; Humans; Papillomaviridae - classification; Papillomaviridae - genetics; Papillomaviridae - isolation & purification; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - virology
• ISSN: 1386-6532; 1873-5967
• DOI: 10.1016/S1386-6532(02)00181-6

Background: Epidemiological and virological surveys suggest that the HPV presence is not enough condition to generate anogenital cancer, others factors (genetic, environmental, hormonal, etc) may have an important role. Mutations of ras genes were observed in several human neoplasias, including cervical cancer. Objective: The aim of the study was to assess the frequency of Ha-ras oncogene mutations in cervical intraepithelial neoplasia (CIN) grade III and invasive squamous cell carcinomas and to examine this genetic factor in relation to HPV infection and the clinical evolution of cervical lesions. Study design: They were selected for (a) evaluation of the frequency of Ha-ras mutations: 39 cases of invasive carcinomas (InCa), 47 CIN III and 12 normal tissues taken from areas adjacent to the tumor (NT). (b) Retrospective follow-up: 18 cases of lesion progression; 9 cases of persistence and 12 of regression to mature or immature metaplasia after specific treatment. All biopsies obtained from each patient during the follow-up done between 5 and 10 years were included. HPV typing and scanning of possible mutations in Ha-ras were made by single-strand conformation polymorphism analysis/polymerase chain reaction. Results: HPV–DNA was detected in 95% of InCa and 84% of CIN III; HPV 16/18 was found in 65% of patients, mainly associated with persistent infection and lesion progression. The undetermined HPV types (18%) could indicate the circulation in our country of types other than those screened (6, 11, 16, 18, 31 and 33). Twenty percent of CIN III and 41% of InCa had patterns compatible with Ha-ras mutations. Mutated Ha-ras was detected in 61 and 44% of progression and persistence cases, respectively, including early stages of progression. Conclusions: Ha-ras mutations were detected in CIN II–III lesions; in mutated cases, the progression took place in under 2 years, then this detection may be an early predictive marker of rapid progression.