Alonio L V, Dalbert D, Picconi M A, Cervantes Vazquez G, García Carrancá A, Distefano A L, Mural J, Bartt O, Bazan G, Teyssie A R
Instituto Nacional de Enfermedades Infecciosas, ANLIS Dr. Carlos G. Malbrán, Buenos Aires,
Medicina (B Aires). 2000;60(6):895-901.
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.
本研究旨在通过随机试验调查宫颈癌及癌前病变中人类乳头瘤病毒（HPV）的感染频率以及Ha-ras癌基因和肿瘤抑制基因p53的突变情况。研究共纳入30例浸润性癌（IC）、36例宫颈上皮内瘤变III级（CIN III）以及12例肿瘤旁正常组织（NT）。采用单链构象多态性聚合酶链反应（SSCP-PCR）对HPV进行分型，并检测Ha-ras和p53基因可能存在的突变。IC病例中HPV阳性率为93%，Ha-ras基因突变导致迁移率改变的占41%，p53基因突变的占17%；而在CIN III中，这些百分比分别为80%、18%和11%。正常组织中HPV感染率为17%。所有Ha-ras基因突变样本均为HPV阳性，但33%的p53基因突变病例为HPV阴性。所有突变均为杂合突变。HPV 16型比HPV 18型更为常见（44%比15%），未确定型HPV的高比例（18%）表明我国存在不同于检测的HPV对照型（6、11、16、18、31和33型）的其他类型，可能为变异型或混合感染。p53基因突变的低频率（17%）进一步支持了HPV使野生型p53失活可能在宫颈癌发病机制中起主要作用这一观点。由于在HPV相关的癌前病变中发现了Ha-ras基因突变，我们推测它是疾病进展的早期标志物。我们的研究结果为高危型HPV与癌基因激活在子宫颈癌发生过程中的相互作用提供了更多证据。
