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锯齿状腺瘤中的基因改变:与传统腺瘤和增生性息肉的比较。

Genetic alterations in serrated adenomas: comparison to conventional adenomas and hyperplastic polyps.

作者信息

Fogt Franz, Brien Thomas, Brown Charlotte A, Hartmann Christopher J, Zimmerman Robert L, Odze Robert D

机构信息

Department of Pathology, Presbyterian Medical Center, University of Pennsylvania, Philadelphia, PA 19104, USA.

出版信息

Hum Pathol. 2002 Jan;33(1):87-91. doi: 10.1053/hupa.2002.30377.

DOI:10.1053/hupa.2002.30377
PMID:11823977
Abstract

Serrated adenoma is a recently described entity characterized by the presence of a hyperplastic (serrated) growth pattern combined with cytologic features of dysplasia. In contrast to conventional (nonserrated) adenomas, the molecular features of serrated adenomas have been poorly studied. Thus, it remains unclear if serrated adenomas are simply a morphologic variant of conventional adenomas or represent a different biologic entity. In this study, 46 serrated adenomas from 39 patients, 32 conventional (nonserrated) adenomas from 31 patients, and 18 hyperplastic polyps from 16 patients were evaluated for loss of heterozygosity (LOH) of APC, p53, p16, and 3p and for K-ras mutations of codons 12, 13, and 61 by polymerase chain reaction (PCR) analysis. Serrated adenomas demonstrated LOH of at least one genetic locus in 32.6% of cases. LOH of the APC gene, 3p, p53, and p16 was seen in 19.4%, 14.2%, 9.3%, and 13.8% of cases, respectively. K-ras mutations were observed in 18% of cases. Similar to serrated adenomas, conventional adenomas demonstrated at least one LOH event in 37.5% of cases and K-ras mutations in another 19% of cases. LOH of APC, 3p, p53, and p16 was observed in 22%, 33%, 5.8%, and 13.4% of cases, respectively. There were no significant differences in either the total number of genetic events or the presence of LOH of any of the individual markers between serrated adenomas and conventional adenomas. However, hyperplastic polyps showed LOH in 22% of cases and a single K-ras mutation (11%). The prevalence of LOH in hyperplastic polyps was lower than both serrated adenomas and conventional adenomas (P < .05). These results support the hypothesis that serrated adenomas represent a biologically similar morphologic variant of conventional adenomas.

摘要

锯齿状腺瘤是一种最近被描述的病变,其特征为存在增生性(锯齿状)生长模式并伴有发育异常的细胞学特征。与传统(非锯齿状)腺瘤不同,锯齿状腺瘤的分子特征研究较少。因此,目前尚不清楚锯齿状腺瘤是否仅仅是传统腺瘤的一种形态学变异,还是代表一种不同的生物学实体。在本研究中,对来自39例患者的46个锯齿状腺瘤、来自31例患者的32个传统(非锯齿状)腺瘤以及来自16例患者的18个增生性息肉进行了评估,通过聚合酶链反应(PCR)分析检测APC、p53、p16和3p的杂合性缺失(LOH)以及密码子12、13和61的K-ras突变。锯齿状腺瘤在32.6%的病例中显示至少一个基因位点的LOH。APC基因、3p、p53和p16的LOH分别见于19.4%、14.2%、9.3%和13.8%的病例。18%的病例观察到K-ras突变。与锯齿状腺瘤相似,传统腺瘤在37.5%的病例中显示至少一个LOH事件,另外19%的病例有K-ras突变。APC、3p、p53和p16的LOH分别见于22%、33%、5.8%和13.4%的病例。锯齿状腺瘤和传统腺瘤在遗传事件总数或任何单个标志物的LOH存在方面均无显著差异。然而,增生性息肉在22%的病例中显示LOH,并有一个单一的K-ras突变(11%)。增生性息肉中LOH的发生率低于锯齿状腺瘤和传统腺瘤(P < .05)。这些结果支持了锯齿状腺瘤代表传统腺瘤生物学上相似的形态学变异这一假说。

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