Horikoshi Motoko, Kina Katsunari, Ishi Kazuhisa, Izumi Hiroshi, Kunii Yuiko, Nojima Michio
Department of Clinical Pathology, Juntendo University Urayasu Hospital, Urayasu 279-0021.
Rinsho Byori. 2005 Jun;53(6):494-8.
Human papilloma virus (HPV) is the most important factor in the oncogenic mechanism of cervical tumor. Furthermore, in a separate multi-stage process, abnormality in cell cycle kinetics has been demonstrated. In order to elucidate the oncogenic mechanism, we examined the relationship between cervical carcinoma and HPV infection, and also investigated the expression of p53 and p21 proteins as well as the cell proliferation capability by detecting Ki-67, and analyzed the correlations of these factors.
We studied the biopsy specimens from 107 patients of chronic cervicitis, cervical intraepithelial neoplasia and squamous cell carcinoma (SCC). HPV DNA was detected by the hybrid capture method. Immunostaining by LSAB procedures were performed using antibodies to p53 protein, p21 and MIB-1. The PCR-denaturing gradient gel electrophoresis (DGGE) method was used to search for mutation in exons 5, 6, 7 and 8 of p53.
Of 107 cases studied, high-oncogenic HPV was detected in 80 cases (74.8%) with a particularly high prevalence in SCC. No correlation was observed between HPV infection and expression of p53, p21 or Ki-67. The degree of positivity of Ki-67 expression tended to be higher with disease progression. Cases strongly positive (2+) for p53 and p21 proteins were weakly positive for Ki-67, and cases positive (1+) or negative for p53 and p21 were strongly positive for Ki-67.
In oncogenesis of cervical carcinoma, p53 protein, p21 protein and HPV may act separately as independent factors in some cases, and there is a strong possibility that other factors are involved.
人乳头瘤病毒(HPV)是宫颈肿瘤致癌机制中最重要的因素。此外,在一个单独的多阶段过程中,已证实细胞周期动力学存在异常。为了阐明致癌机制,我们研究了宫颈癌与HPV感染之间的关系,还通过检测Ki-67来研究p53和p21蛋白的表达以及细胞增殖能力,并分析了这些因素之间的相关性。
我们研究了107例慢性宫颈炎、宫颈上皮内瘤变和鳞状细胞癌(SCC)患者的活检标本。采用杂交捕获法检测HPV DNA。使用针对p53蛋白、p21和MIB-1的抗体,通过LSAB程序进行免疫染色。采用PCR-变性梯度凝胶电泳(DGGE)法检测p53外显子5、6、7和8中的突变。
在研究的107例病例中,80例(74.8%)检测到高致癌性HPV,在SCC中患病率特别高。未观察到HPV感染与p53、p21或Ki-67表达之间的相关性。Ki-67表达的阳性程度倾向于随着疾病进展而升高。p53和p21蛋白强阳性(2+)的病例Ki-67弱阳性,p53和p21阳性(1+)或阴性的病例Ki-67强阳性。
在宫颈癌的发生过程中,p53蛋白、p21蛋白和HPV在某些情况下可能分别作为独立因素起作用,并且很有可能涉及其他因素。