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克隆性分析表明 STK11 基因突变参与了小叶宫颈腺上皮增生(LEGH)向微偏腺癌(MDA)的进展。

Clonality analysis suggests that STK11 gene mutations are involved in progression of lobular endocervical glandular hyperplasia (LEGH) to minimal deviation adenocarcinoma (MDA).

机构信息

Department of Obstetrics and Gynecology, School of Medicine, Shinshu University, 3-1-1 Asahi, Matsumoto 390-8621, Japan.

出版信息

Virchows Arch. 2013 Jun;462(6):645-51. doi: 10.1007/s00428-013-1417-1. Epub 2013 May 4.

Abstract

Lobular endocervical glandular hyperplasia (LEGH) is a benign proliferative disease of cervical glands. Although histological resemblance of minimal deviation adenocarcinoma (MDA) to LEGH and frequent association of LEGH with MDA have been reported, it still remains unclear whether LEGH is a precancerous lesion of MDA. The present study was undertaken to examine the pathogenetic relationship between LEGH and MDA using a clonality analysis and mutational analyses of the STK11 gene, of which mutations have been reported in MDA. Of nine cases of LEGH only, four were polyclonal and five were monoclonal in composition. Of six LEGH lesions associated with MDA or adenocarcinoma, two were polyclonal and four were monoclonal. In cases of MDA or adenocarcinoma coexisting with LEGH, the patterns of X chromosome inactivation in malignant lesions were identical to those in coexisting LEGH lesions. A mutation of STK11 was only identified in one MDA, but not in LEGH. These results indicate that a subset of LEGH may be a precursor to malignant tumors including MDA and that a mutation of STK11 may be involved in progression of LEGH to MDA.

摘要

宫颈管腺上皮内增生(LEGH)是宫颈腺体的一种良性增生性疾病。虽然已有报道显示,微小偏离型腺癌(MDA)在组织学上类似于 LEGH,且 LEGH 常与 MDA 相关,但 LEGH 是否为 MDA 的癌前病变仍不清楚。本研究通过对 STK11 基因突变的克隆性分析,旨在探讨 LEGH 和 MDA 之间的发病关系,因为已有报道称 MDA 存在该基因突变。9 例 LEGH 中,仅 4 例为多克隆,5 例为单克隆。6 例 LEGH 病变伴 MDA 或腺癌,其中 2 例为多克隆,4 例为单克隆。在 LEGH 与 MDA 或腺癌共存的病例中,恶性病变的 X 染色体失活模式与共存的 LEGH 病变相同。仅在一个 MDA 中发现了 STK11 的突变,而在 LEGH 中没有发现。这些结果表明,一部分 LEGH 可能是 MDA 等恶性肿瘤的前体,而 STK11 的突变可能参与了 LEGH 向 MDA 的进展。

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