RESUMO
The aim of this study w trial randomized as to investigate the frequencies of human papillomavirus (HPV) and mutation in Ha-ras oncogene and tumour suppressor p53 gene in cervical cancer and precursor lesions. A total of 30 invasive carcinomas (IC), 36 cervical intraepithelial neoplasia grade III (CIN III) and 12 normal tissues adjacent to the tumor (NT) were included. HPV typification and scanning of possible mutations in Ha-ras and p 53 genes were made by SSCP-PCR. The IC cases showed 93% HPV positivity, 41% having mobility shifts for Ha-ras mutations and 17% for p53 mutations while in CIN III, these percentages were 80%, 18% and 11%, respectively. In normal tissues HPV frequency was 17%. All Ha-ras mutated samples were HPV positive but 33% of p53 mutated cases were HPV negative. All mutations were heterozygous. HPV 16 was more prevalent (44%) than HPV 18 (15%) and the high rate of undetermined HPV types (18%) would indicate the circulation in our country of other types different from the assayed HPV controls (6, 11, 16, 18, 31 and 33), being variants or mixed infections. The low frequency of p53 mutations (17%) strengthens the view that wild type p53 inactivation by HPV probably plays a major role in the pathogenesis of cervical cancer. Because mutated Ha-ras was found in HPV associated premalignant lesions, we speculate that it represents an early marker for progression. Our findings provide additional evidence for an interactive effect between high risk types of HPV and oncogene activation in the development of uterine cervical cancer.
Assuntos
Genes p53/genética , Genes ras/genética , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Infecções Tumorais por Vírus/virologia , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/virologia , DNA Viral/genética , Feminino , Humanos , Mutação/genética , Infecções por Papillomavirus/genética , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Neoplasias do Colo do Útero/genéticaRESUMO
The aim of this study w trial randomized as to investigate the frequencies of human papillomavirus (HPV) and mutation in Ha-ras oncogene and tumour suppressor p53 gene in cervical cancer and precursor lesions. A total of 30 invasive carcinomas (IC), 36 cervical intraepithelial neoplasia grade III (CIN III) and 12 normal tissues adjacent to the tumor (NT) were included. HPV typification and scanning of possible mutations in Ha-ras and p 53 genes were made by SSCP-PCR. The IC cases showed 93
HPV positivity, 41
having mobility shifts for Ha-ras mutations and 17
for p53 mutations while in CIN III, these percentages were 80
, 18
and 11
, respectively. In normal tissues HPV frequency was 17
. All Ha-ras mutated samples were HPV positive but 33
of p53 mutated cases were HPV negative. All mutations were heterozygous. HPV 16 was more prevalent (44
) than HPV 18 (15
) and the high rate of undetermined HPV types (18
) would indicate the circulation in our country of other types different from the assayed HPV controls (6, 11, 16, 18, 31 and 33), being variants or mixed infections. The low frequency of p53 mutations (17
) strengthens the view that wild type p53 inactivation by HPV probably plays a major role in the pathogenesis of cervical cancer. Because mutated Ha-ras was found in HPV associated premalignant lesions, we speculate that it represents an early marker for progression. Our findings provide additional evidence for an interactive effect between high risk types of HPV and oncogene activation in the development of uterine cervical cancer.
Assuntos
Humanos , Feminino , Gravidez , Carcinoma in Situ/cirurgia , Conização/efeitos adversos , Neoplasias do Colo do Útero/cirurgia , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/terapia , Eletrocirurgia , Eletrocirurgia/efeitos adversos , Eletrocirurgia/classificação , Neoplasias do Colo do Útero/terapiaAssuntos
Humanos , Feminino , Gravidez , Neoplasias do Colo do Útero/cirurgia , Conização/efeitos adversos , Carcinoma in Situ/cirurgia , Neoplasias do Colo do Útero/terapia , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/terapia , Eletrocirurgia/classificação , Eletrocirurgia/métodos , Eletrocirurgia/efeitos adversosRESUMO
OBJECTIVE: The aim of this study was to identify human papillomavirus (HPV) in cervical intraepithelial neoplasia (CIN) lesions and to evaluate the persistence of viral DNA after diathermic large loop excision (DLLE) treatment. STUDY DESIGN: Biopsies from 36 patients with low- and high-grade CIN lesions were studied before and after DLLE treatment looking for HPV sequences. DNA was extracted to perform a radioactive polymerase chain reaction (PCR) using GP 5,6 generic primers. PCR products were analyzed by the single-stranded conformational polymorphism (SSCP) which is a simultaneous detection and typing method. Dot-blot hybridization with generic and type-specific biotinylated oligonucleotide probes was applied in some cases. RESULTS: HPV DNA was found in all pretreatment samples, and the viral type was identified in 80% of them, HPV 16 being the most prevalent. The viral type coincided with that detected in the first biopsy in all except one case. Seventy five percent of the patients (27 cases) were negative for CIN at follow up, but 50% of them remained HPV DNA positive. CONCLUSION: DLLE treatment was effective in removing the CIN lesion but not the HPV. This fact points out the need to asses the presence of HPV in DNA during the follow-up, since viral persistence has been considered a high risk factor for recurrence and/or malignant transformation.
