Seven of 12 subjects who had SRCC reported no diagnoses of DGC in first-degree relatives and did not meet established criteria for CDH1 analysis based on a 3-generation family pedigree.
Additionally, CDH1 testing could be considered in patients with bilateral or familial LBC before the age of 50, patients with DGC and cleft lip/palate, and those with precursor lesions for signet ring cell carcinoma.
Signet ring cell carcinoma foci were identified in 14 of 22 (63.6%) patients with confirmed CDH1 germline mutations and 2 of 7 (28.6%) with no pathogenic mutation identified.
A 51- year old woman, with known CDH1 mutation carrier status and a prior history of lobular breast carcinoma underwent prophylactic total gastrectomy which revealed multifocal intramucosal signet ring cell carcinoma.
The earliest indications of cancer in the stomachs of CDH1 mutation carriers are microscopic foci of intramucosal signet-ring cell carcinoma (SRCC; designated "eHDGC").
Our study indicates that superficial intramucosal signet ring carcinoma, although widespread, is predominantly located in the proximal one third of the stomach in patients with E-cadherin gene mutations.
Immunohistochemical studies of gastric ECL cell tumors showed a largely diminished E-cadherin expression in comparison to gastric surface mucosa cells and a loss of E-cadherin expression in the cells of the signet-ring carcinoma.