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低级别胃腺瘤/发育异常:表型表达、DNA倍体模式以及与APC基因相关的微卫星处的杂合性缺失

Low-grade gastric adenomas/dysplasias: phenotypic expression, DNA ploidy pattern, and LOH at microsatellites linked to the APC gene.

作者信息

Tanaka Aiko, Takemura-Tsukashita Shizuki, Kushima Ryoji, Sugihara Hiroyuki, Fujiyama Yoshihide, Hattori Takanori

机构信息

Department of Pathology, Shiga University of Medical Science, Otsu, Japan; Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan.

出版信息

Pathol Res Pract. 2008;204(1):1-9. doi: 10.1016/j.prp.2007.08.014. Epub 2007 Oct 25.

DOI:10.1016/j.prp.2007.08.014
PMID:17964080
Abstract

The adenoma-adenocarcinoma sequence in the colon is generally accepted. Regarding the stomach, however, opinions about tumorigenesis are different. We analyzed the phenotypes, DNA ploidy patterns, and microsatellite regions linked to adenomatous polyposis coli (APC) gene on chromosome 5q of low-grade gastric adenomas/dysplasias, Vienna Category 3, to investigate whether these lesions have the potential to become adenocarcinomas. Phenotypes were determined by immunohistochemical staining with monoclonal antibodies MUC2, MUC5AC, MUC6, CD10, and Cdx2. DNA ploidy patterns were determined by static cytofluorometry. Microsatellite analyses were performed using Genescan on genetic analyzer ABI PRISM 310. None of the 15 cases showed coexisting high-grade adenomas/dysplasias or adenocarcinoma. Eighty percent of the cases had the complete intestinal phenotype, and the remainder showed slight MUC6 positivity for the intestinal phenotype. All cases were positive for Cdx2 and showed diploid DNA. In addition, 46.7% of the cases exhibited loss of heterozygosity (LOH) of chromosome 5q. Except for one case, 5q-LOH was detected at a single locus in cases with the complete intestinal phenotype. According to previous studies, most gastric adenocarcinomas have the gastric phenotype and no 5q-LOH. These results suggest that low-grade gastric adenomas/dysplasias, Vienna category 3, seldom progress to gastric adenocarcinomas of the differentiated type.

摘要

结肠中的腺瘤-腺癌序列已被广泛接受。然而,关于胃的肿瘤发生,观点却有所不同。我们分析了低级别胃腺瘤/发育异常(维也纳分类3类)5号染色体上与腺瘤性息肉病 coli(APC)基因相关的表型、DNA倍体模式和微卫星区域,以研究这些病变是否有发展为腺癌的潜力。通过使用单克隆抗体MUC2、MUC5AC、MUC6、CD10和Cdx2进行免疫组织化学染色来确定表型。通过静态细胞荧光测定法确定DNA倍体模式。使用基因扫描在基因分析仪ABI PRISM 310上进行微卫星分析。15例病例中均未显示存在高级别腺瘤/发育异常或腺癌。80%的病例具有完全的肠型表型,其余病例显示肠型表型有轻微的MUC6阳性。所有病例的Cdx2均为阳性,且显示二倍体DNA。此外,46.7%的病例表现出5号染色体q臂杂合性缺失(LOH)。除1例病例外,在具有完全肠型表型的病例中,5q-LOH在单个位点被检测到。根据先前的研究,大多数胃腺癌具有胃型表型且无5q-LOH。这些结果表明,维也纳分类3类的低级别胃腺瘤/发育异常很少进展为分化型胃腺癌。

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