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胰腺导管内黏液高分泌性肿瘤中的K-ras突变与p53蛋白积聚

K-ras mutation and p53 protein accumulation in intraductal mucin-hypersecreting neoplasms of the pancreas.

作者信息

Satoh K, Shimosegawa T, Moriizumi S, Koizumi M, Toyota T

机构信息

Third Department of Internal Medicine, Tohoku University School of Medicine, Miyagi, Japan.

出版信息

Pancreas. 1996 May;12(4):362-8. doi: 10.1097/00006676-199605000-00007.

DOI:10.1097/00006676-199605000-00007
PMID:8740403
Abstract

Intraductal mucin-hypersecreting neoplasm of the pancreas (IMHN) is a unique tumor that is composed of tumor cells with different cell atypia. K-ras and p53 alterations have been shown to occur in pancreatic duct cell carcinoma (PDC), but they have not been well documented in the individual lesion of IMHN. The aim of this study was to examine the relation of the genetic alterations of K-ras and p53 in IMHN to the tumorigenesis of the pancreas. In 32 microscopically dissected lesions of seven cases of IMHN, the K-ras mutation was investigated by primer-mediated, mutant-enriched, polymerase chain reaction-restriction fragment length polymorphism. Mutant p53 expression was examined in the adjacent serial sections by immunohistochemistry. In IMHN, alterations of K-ras and p53 were frequently observed (71.9 and 50%, respectively). The frequency became higher as the grade of cell atypia increased. Simultaneous alterations of the two genes were detected in carcinoma and its accompanying hyperplastic and dysplastic lesions. It is suggested that alterations of K-ras and p53 may be early events in the tumorigenesis of IMHN and may cooperate to produce neoplastic transformation of the pancreatic duct epithelium.

摘要

胰腺导管内黏液高分泌性肿瘤(IMHN)是一种独特的肿瘤,由具有不同细胞异型性的肿瘤细胞组成。K-ras和p53改变已被证实在胰腺导管细胞癌(PDC)中出现,但在IMHN的单个病变中尚未得到充分记录。本研究的目的是探讨IMHN中K-ras和p53基因改变与胰腺肿瘤发生的关系。在7例IMHN的32个经显微镜解剖的病变中,通过引物介导的、突变富集的聚合酶链反应-限制性片段长度多态性检测K-ras突变。在相邻连续切片中通过免疫组织化学检测突变型p53表达。在IMHN中,经常观察到K-ras和p53改变(分别为71.9%和50%)。随着细胞异型性程度的增加,频率升高。在癌及其伴随的增生和发育异常病变中检测到两个基因的同时改变。提示K-ras和p53改变可能是IMHN肿瘤发生的早期事件,并可能协同作用导致胰腺导管上皮的肿瘤转化。

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