Model of the early development of diffuse gastric cancer in E-cadherin mutation carriers and its implications for patient screening
Model of the early development of diffuse gastric cancer in E-cadherin mutation carriers and its implications for patient screening
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DOI：
10.1002/path.1564
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发表时间：
2004-06-01
影响因子：
7.3
通讯作者：
Sobrinho-Simoes, M
中科院分区：
文献类型：
--
作者：
Carneiro, F;Huntsman, DG;Sobrinho-Simoes, M
遗传性弥漫性胃癌（HDGC）是一种家族性癌症综合征，在30-40%的病例中，由E-cadherin/CDH 1基因的种系突变引起。先前已报道，在生殖系E-钙粘蛋白突变携带者的10例预防性胃切除术中，有10例存在临床检测不到的早期胃癌。在本研究中，我们绘制了这10个胃中9个的浸润性癌分布的详细地图，并搜索了HDGC的前驱病变。9例胃切除标本中有1 ~ 161个早期弥漫性胃癌灶，占胃粘膜的0.005-2.96%。7例标本含有局灶性原位印戒癌。在胃小凹/腺体的上皮衬里下观察到印戒细胞的Pagetoid扩散。所有病例均无幽门螺杆菌微生物和相关病理学。胃切除术标本的二维图像显示整个胃粘膜的病变，没有胃窦聚集的证据。胃切除术标本中癌症的分布和大小表明，随机或地理靶向活检的标准内镜筛查不太可能为高危个体提供足够敏感的临床筛查。原位前体的印戒癌被确定，并提出了一个模型的肿瘤进展的设置HDGC。版权所有（C）2004大不列颠和爱尔兰病理学会。出版社：John Wiley Sons，Ltd
Hereditary diffuse gastric cancer (HDGC) is a familial cancer syndrome caused, in 30-40% of cases, by germline mutations of the E-cadherin/CDH1 gene. The presence of clinically undetectable early gastric cancers has been previously reported in ten of ten prophylactic gastrectomies from germline E-cadherin mutation carriers. In the present study, detailed maps of the distribution of invasive cancers in nine of these ten stomachs were produced and precursor lesions of HDGC searched for. The nine gastrectomy specimens contained from 1 to 161 foci of early diffuse gastric cancer, occupying 0.005-2.96% of the gastric mucosa. Seven specimens contained focal in situ signet ring carcinoma. Pagetoid spread of signet ring cells was observed beneath the epithelial lining of gastric foveolae/glands. Helicobacter pylori organisms and associated pathology were absent from all cases. Two-dimensional maps of the gastrectomy specimens revealed lesions throughout the gastric mucosa without evidence of antral clustering. The distribution and size of the cancers in the gastrectomy specimens indicate that standard endoscopic screening with random or geographically targeted biopsies is unlikely to provide sufficiently sensitive clinical screening for at-risk individuals. An in situ precursor of signet ring carcinoma was identified and a model for neoplastic progression in the setting of HDGC is proposed. Copyright (C) 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley Sons, Ltd.