Authors
Ophir Gilad, Christine M Drogan, Emma Keel, Guimin Gao, Carol Swallow, Anand Govindarajan, Savtaj Brar, Melissa Heller, Taylor Apostolico, Michelle F Jacobs, Kebire Gofar, Beth Dudley, Eve Karloski, Conner Lombardi, Michelle Springer, Souvik Saha, Devin Cox, Benjamin A Lerner, George Hanna, Yana Chertock, Afshin Khan, Sarah Ertan, Kimberly Hilfrank, Sheila D Rustgi, Aparajita Singh, Michael J Hall, Xavier Llor, Ajay Bansal, Swati G Patel, Randall E Brand, Maegan E Roberts, Peter P Stanich, Elena Stoffel, Bryson W Katona, Melyssa Aronson, Sonia S Kupfer
Published in
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. Aug 16, 2026. Epub Aug 16, 2026.
Abstract
Gastric cancer surveillance in CDH1 pathogenic variant carriers is challenging, as predictors of localized (stage T1a) and advanced (stage >T1a) signet ring cell carcinoma (SRCC) are not well defined. We established the Group of investigAtors STriving toward Research In CDH1 (GASTRIC) consortium to identify clinicopathological factors associated with localized and advanced SRCC.
A retrospective observational study (1998-2025) of CDH1 carriers across twelve academic centers was performed. Clinical, endoscopic, and pathological data were compared between carriers with and without SRCC on endoscopy, and between those with advanced versus localized or no cancer on gastrectomy specimens.
Overall, 390 CDH1 carriers from 235 families were included. Presence of biopsy-detected SRCCs on endoscopy was significantly associated with thickened folds, nodularity, masses, and intestinal metaplasia, while gastritis was negatively associated. Of 196 carriers (52.4%) undergoing gastrectomy, 11 (5.6%) had advanced cancers, 10(90.9%) of which showed endoscopic abnormalities. Identification of biopsy-detected SRCC on baseline endoscopy was the most sensitive feature for advanced disease (0.81) but had moderate specificity (0.74) and low positive predictive value (0.21), whereas masses and thickened folds were highly specific (0.99 and 0.96, respectively) but less sensitive. Negative predictive values were high (0.94-1.0), while positive predictive values were modest (0.13-0.66). On multivariable analysis, masses and SRCC foci on baseline endoscopy were independent predictors of advanced disease.
Among CDH1 carriers, absence of endoscopic findings was reassuring, whereas significance of detected endoscopic and pathological abnormalities was less certain. Advanced cancer occurred in a small number of carriers, with endoscopic abnormalities in nearly all cases. Endoscopic surveillance might be an alternative to surgery in carriers without worrisome mucosal findings.
PMID:
42604658
Bibliographic data and abstract were imported from PubMed on 17 Aug 2026.
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