Model of the early development of diffuse gastric cancer in E-cadherin mutation carriers and its implications for patient screening

被引:189
作者
Carneiro, F
Huntsman, DG
Smyrk, TC
Owen, DA
Seruca, R
Pharoah, P
Caldas, C
Sobrinho-Simoes, M
机构
[1] IPATIMUP, P-4200465 Oporto, Portugal
[2] Univ Porto, HS Joao, Fac Med, P-4100 Oporto, Portugal
[3] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada
[4] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada
[5] Mayo Clin, Dept Pathol, Rochester, MN USA
[6] Canc Res UK, Dept Oncol, Cambridge, England
[7] Strangeways Res Lab, Cambridge CB1 4RN, England
[8] Univ Cambridge, Dept Oncol, Cambridge, England
[9] Addenbrookes Hosp, Hutchinson MRC Res Ctr, Cambridge, England
关键词
E-cadherin; germline mutations; hereditary gastric cancer; pagetoid spread; screening;
D O I
10.1002/path.1564
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:681 / 687
页数:7
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