Nishimura M, Furumoto H, Kato T, Kamada M, Aono T
Department of Obstetrics and Gynecology, School of Medicine, University of Tokushima, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
Gynecol Oncol. 2000 Nov;79(2):201-6. doi: 10.1006/gyno.2000.5940.
The purpose of this study was to elucidate the role of genetic instability and LOH in the progression of cervical cancer and also to analyze for correlations between these genetic abnormalities and the clinicopathological characteristics of cervical cancers.
Seventy-two DNA samples were obtained from 29 carcinoma in situ, 8 microinvasive carcinoma, and 35 invasive cancers. Seven highly polymorphic microsatellite markers representing the chromosome 3p, 6p, and 6q arms were examined by PCR amplification.
Microsatellite instability was detected in 8 of 35 (22.9%) invasive cancers and in 1 of 37 (2.7%) early stage cancers (microinvasive cancer and carcinoma in situ). The incidence of MI was statistically higher in invasive cancers (P < 0.02). On the other hand, loss of heterozygosity (LOH) of chromosome 3p was identified in 6/41 (14.6%) invasive cancers and in 3/27 (11.1%) carcinomas in situ. There was no statistical difference between the two groups. There were no significant correlations between the presence of MI or 3p LOH and clinicopathological characteristics including the histological type, FIGO stage, depth of myometrial invasion, lymphovascular involvement, lymph node metastasis, and recurrence.
Our results indicate that genomic instability is a late event during the carcinogenesis of cervical cancer and is associated with the conversion of cervical intraepithelial neoplasia to an invasive phenotype. To the contrary, LOH of chromosome 3p plays an early role in the development of cervical intraepithelial neoplasia. No significant correlation was observed between the presence of MI or LOH and clinicopathological characteristics.
本研究旨在阐明基因不稳定性和杂合性缺失（LOH）在宫颈癌进展中的作用，并分析这些基因异常与宫颈癌临床病理特征之间的相关性。
从29例原位癌、8例微浸润癌和35例浸润癌中获取72份DNA样本。通过PCR扩增检测代表3号染色体p臂、6号染色体p臂和6号染色体q臂的7个高度多态性微卫星标记。
在35例（22.9%）浸润癌中有8例检测到微卫星不稳定性，在37例早期癌（微浸润癌和原位癌）中有1例（2.7%）检测到微卫星不稳定性。浸润癌中微卫星不稳定性的发生率在统计学上更高（P < 0.02）。另一方面，在6/41（14.6%）的浸润癌和3/27（11.1%）的原位癌中发现3号染色体p臂杂合性缺失（LOH）。两组之间无统计学差异。微卫星不稳定性（MI）或3号染色体p臂LOH的存在与包括组织学类型、国际妇产科联盟（FIGO）分期、肌层浸润深度、淋巴管受累、淋巴结转移和复发在内的临床病理特征之间无显著相关性。
我们的结果表明，基因组不稳定性是宫颈癌发生过程中的晚期事件，与宫颈上皮内瘤变向浸润性表型的转变有关。相反，3号染色体p臂的杂合性缺失在宫颈上皮内瘤变的发展中起早期作用。未观察到微卫星不稳定性（MI）或杂合性缺失（LOH）的存在与临床病理特征之间有显著相关性。
