Moyret-Lalle C, Marçais C, Jacquemier J, Moles J P, Daver A, Soret J Y, Jeanteur P, Ozturk M, Theillet C
Institut de Génétique Moléculaire de Montpellier, France.
Int J Cancer. 1995 Apr 21;64(2):124-9. doi: 10.1002/ijc.2910640209.
To study the role of ras, p53 genes and HPV virus (16 and 18) in the development of prostate cancer, we analyzed tissue sections from 27 patients affected with carcinomas (stages A to D) and from 24 patients with adenomas. Mutations of H, K and N-ras and p53 (exons 2-9) were studied by SSCP and DNA sequencing. Accumulation of p53 protein was studied by immunohistochemistry on tissue sections. Tumors were also analyzed for the presence of HPV16 and -18 sequences by PCR and DNA hybridization with sequence-specific oligonucleotides. No mutation was found in the three ras genes studied, either in carcinomas or adenomas. By SSCP analysis we identified p53 mutations in only 2 of 19 carcinomas studied, both in exon 7. Immunohistochemical results strongly correlate with the SSCP results: p53 protein was positive in tumors with p53 mutation but not in others; 32% of studied adenomas had detectable HPV16 DNA, while 53% of carcinomas were HPV16+. Among these I presented a p53 mutation. No HPV18 E6 sequence could be detected. Our data show that in prostate tumors from France, mutations of p53 and ras are rare events but that these tumors display detectable HPV16 DNA at a high frequency. The low incidence of p53 mutation, associated to a significant proportion of tumors showing HPV16 DNA, could suggest that in prostate cancer HPV16 infection could participate in p53 inactivation by E6.
为研究ras、p53基因及人乳头瘤病毒（16型和18型）在前列腺癌发生发展中的作用，我们分析了27例患癌（A至D期）患者及24例患腺瘤患者的组织切片。通过单链构象多态性（SSCP）和DNA测序研究H、K和N - ras及p53（外显子2 - 9）的突变情况。通过对组织切片进行免疫组织化学研究p53蛋白的积累情况。还通过聚合酶链反应（PCR）及与序列特异性寡核苷酸的DNA杂交分析肿瘤中HPV16和 - 18序列的存在情况。在所研究的三种ras基因中，无论是癌组织还是腺瘤组织均未发现突变。通过SSCP分析，我们在所研究的19例癌组织中仅在2例中鉴定出p53突变，且均在外显子7。免疫组织化学结果与SSCP结果高度相关：p53突变的肿瘤中p53蛋白呈阳性，其他肿瘤则否；32%的所研究腺瘤可检测到HPV16 DNA，而53%的癌组织HPV16呈阳性。其中1例呈现p53突变。未检测到HPV18 E6序列。我们的数据表明，在法国的前列腺肿瘤中，p53和ras突变很少见，但这些肿瘤中HPV16 DNA的检出频率很高。p53突变的低发生率，与相当比例显示HPV16 DNA的肿瘤相关，这可能提示在前列腺癌中HPV16感染可能通过E6参与p53的失活。
