子宫内膜间质肉瘤中的等位基因不平衡:非肿瘤性正常表现的子宫内膜和子宫肌层组织中常见的基因突变

作     者：Moinfar F Kremser M.-L 侯巍 

出 版 物：《世界核心医学期刊文摘（妇产科学分册）》 (Core Journal in Obstetrics/Gynecology)

年 卷 期：2005年第1卷第5期

页      面：37-38页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：子宫肌层 子宫内膜 基因突变 非肿瘤性 子宫平滑肌瘤 微卫星不稳定性 恶性度 基因异常 不平衡 遗传学改变 

摘      要：Endometrial stromal sarcoma (ESS) is among the rarest primary malignant tumors of the uterus. The aim of this study was to examine the possibility of loss of heterozygosity (LOH) and microsatellite instability (MIS) in different tissue co mponents of ESS. Using PCR, we examined DNA extracts from microdissected tissues of 27 uterus samples containing malignant stromal cells of ESS (20 low grade an d 3 high grade sarcomas)-, benign tumor cells of endometrial stromal nodules (E SN, 4 cases) as well as tumor-free myometrial and endometrial tissues close to and distant from the tumors. Normal cervical tissues (epithelial cells, stroma c ells) were also microdissected and analyzed. Fifteen polymorphic DNA markers (ch romosomes 2p, 3p, 5q, 10q, 11q, 13q, and 17p) were tested to identify possible g enetic alterations. Samples from 10 women with prolapsed uteri without any histo pathologic abnormalities were also selected as controls. While no genetic altera tions could be identified in 12 (44.5%) ESS cases, 15 (55.5%) revealed LOH wit h at least one polymorphic DNA marker. LOH were found in 3 (100%) high-grade s arcomas, 10 (50%) low-grade ESS, and 2 (50%) benignESN. Although LOH was foun d more often in the neoplastic stromal cells, several cases showed concurrent an d independent LOH in the tumor-free myometrial or endometrial tissues either cl ose to or distant from the tumors. The most common genetic abnormality (LOH) was observed at PTEN, a tumor suppressor gene located on chromosome 10q. No tumor w as associated with microsatellite instability (MSI). The control group without a ny histologic abnormalities did not show LOH or MSI. The frequent occurrence of LOH and the lack of MSI suggest that loss of function(s) of tumor suppressor gen es and not mismatch repair deficiency plays a key role in the pathogenesis of en dometrial stromal neoplasms. The concurrent and independent occurrence of LOH in the stromal tumor cells and the tumor-free and normal-appearing myometrial