K-ras mutations appear in the premalignant phase of both microsatellite stable and unstable endometrial carcinogenesis
K-ras mutations appear in the premalignant phase of both microsatellite stable and unstable endometrial carcinogenesis
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DOI：
10.1136/mp.52.5.257
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发表时间：
1999-10-01
期刊：
影响因子：
--
通讯作者：
Enomoto, T
中科院分区：
文献类型：
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作者：
Mutter, GL;Wada, H;Enomoto, T
目的：通过比较正常、癌前病变和恶性组织中的遗传性病变，可以研究子宫内膜肿瘤发生的连续事件。K-ras基因突变在微卫星稳定和不稳定的癌前病变的分布进行了研究，以确定是否这个基因是牵连在两个致瘤pathways. Methods-K-ras基因突变进行了分析，聚合酶链反应-单链构象多态性（PCR-SSCP）和直接测序在匹配的子宫内膜正常，癌前病变（非典型增生），腺癌组织从个别患者。识别癌前病变仅仅由其外观为非典型子宫内膜增生是非常主观的，因此，除了组织病理学评估，我们进行了分子检测（非随机X灭活或克隆改变微卫星）的癌前病变的预期功能，即monoclonity.Results-Equivalent K-ras突变频率被认为是在微卫星稳定（6 33）和不稳定（3 23）癌症。在这两种类型中，单克隆癌前病变中的K-ras突变通常对应于从正常到可疑（12例中的2例）或增生（12例中的10例）的组织学变化。不同的K-ras基因型之间的多个肿瘤组织的个别患者（6例中的2例）是例外的解释，无论是多中心癌前病变，或收购的K-ras突变晚期肿瘤progression. Conclusions-K-ras突变发生在癌前微卫星稳定和不稳定的子宫内膜瘤，有时在收购的功能容易诊断为子宫内膜不典型增生。
Aims-Sequential events of endometrial tumorigenesis can be studied by comparison of genetic lesions seen in normal, premalignant, and malignant tissues. The distribution of k-ras mutations in microsatellite stable and unstable premalignant lesions was studied to determine whether this gene is implicated in both tumorigenic pathways.Methods-K-ras mutations were analysed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing in matched endometrial normal, premalignant (atypical hyperplasias), and adenocarcinoma tissues from individual patients. Identification of precancers solely by their appearance as atypical endometrial hyperplasias is very subjective; therefore, in addition to histopathological assessment, we performed molecular testing (non-random X inactivation or clonal altered microsatellites) for an expected feature of precancers that is, monoclonality.Results-Equivalent K-ras mutation frequencies were seen in microsatellite stable (six of 33) and unstable (three of 23) cancers. In both types, K-ras mutation in monoclonal precancers usually corresponded to a change from normal to an equivocal (two of 12) or hyperplastic (10 of 12) histology. Divergent K-ras genotypes among multiple neoplastic tissues of individual patients (two of six patients) are exceptions explained either by multicentric premalignant disease, or acquisition of K-ras mutation late in neoplastic progression.Conclusions-K-ras mutation occurs in both premalignant microsatellite stable and unstable endometrial neoplasia, sometimes before acquisition of features readily diagnostic as atypical endometrial hyperplasia.