O'Leary J J, Landers R J, Silva I, Uhlmann V, Crowley M, Healy I, Luttich K
Department of Pathology, Cornell University Medical College, New York, USA.
J Clin Pathol. 1998 Aug;51(8):576-82. doi: 10.1136/jcp.51.8.576.
To examine the prevalence of genital type human papilloma virus (HPV) and mutations at codons 12, 13, and 61 in H, Ki, and N-ras in CIN III and early invasive squamous cell carcinomas of the cervix.
Prevalence of HPV was examined in 20 CIN III and 20 stage I and II cervical carcinomas, using non-isotopic in situ hybridisation (NISH) and solution phase polymerase chain reaction (PCR). In addition, mutations at codons 12, 13, and 61 were examined in H, Ki, and N-ras in these CIN III and early invasive squamous cell carcinomas, to assess the prevalence of ras gene point mutations and to define where in the pathobiology of squamous cell carcinoma such events occur. A non-isotopic PCR/RFLP assay was used to define these mutations.
Of the 20 CIN IIIs examined, 19 contained HPV 16 DNA sequences by PCR and NISH. Dual infection was not uncovered. The 20 early (stage I and II) invasive squamous cell carcinomas showed predominant HPV 16 positivity (17/20), with one case HPV 18 positive, confirmed on PCR and NISH. Activating mutations were not identified in any of the CIN III cases. Only one stage I, HPV 16 positive carcinoma showed an activating mutation in H-ras codon 12, which was not present in adjacent normal ectocervical mucosa from the same patient.
ras Activation does not appear to occur in conjunction with HPV infection, particularly of HPV 16 infected high grade cervical intraepithelial neoplasia, or to occur commonly in early cervical squamous cell carcinoma. The postulated model of HPV linked carcinogenesis suggests malfunctional control of viral transcription as a necessary component of neoplastic progression. It is also clear that host gene alterations are equally necessary for HPV linked carcinogenesis to occur.
检测宫颈上皮内瘤变III级（CIN III）和早期浸润性鳞状细胞癌中生殖器型人乳头瘤病毒（HPV）的流行情况以及H、Ki和N-ras基因第12、13和61密码子的突变情况。
采用非同位素原位杂交（NISH）和液相聚合酶链反应（PCR）检测20例CIN III以及20例I期和II期宫颈癌中HPV的流行情况。此外，检测这些CIN III和早期浸润性鳞状细胞癌中H、Ki和N-ras基因第12、13和61密码子的突变情况，以评估ras基因点突变的流行情况，并确定这些事件在鳞状细胞癌病理生物学过程中的发生位置。采用非同位素PCR/RFLP分析方法来确定这些突变。
在检测的20例CIN III中，通过PCR和NISH检测发现19例含有HPV 16 DNA序列。未发现双重感染。20例早期（I期和II期）浸润性鳞状细胞癌主要表现为HPV 16阳性（17/20），1例HPV 18阳性，经PCR和NISH证实。在任何CIN III病例中均未发现激活突变。仅1例I期HPV 16阳性癌显示H-ras基因第12密码子有激活突变，而同一患者相邻的正常宫颈外膜黏膜中未出现该突变。
ras激活似乎并非与HPV感染同时发生，尤其是HPV 16感染的高级别宫颈上皮内瘤变，也并非在早期宫颈鳞状细胞癌中常见。假定的HPV相关致癌模型表明，病毒转录的功能失调是肿瘤进展的必要组成部分。同样明显的是，宿主基因改变对于HPV相关致癌作用的发生也是必不可少的。
