Overview on new progress of hereditary diffuse gastric cancer with CDH1 variants.

Hereditary diffuse gastric cancer (HDGC), comprising 1%-3% of gastric malignances, has been associated with CDH1 variants. Accumulating evidence has demonstrated more than 100 germline CDH1 variant types. E-cadherin encoded by the CDH1 gene serves as a tumor suppressor protein. CDH1 promoter hypermethylation and other molecular mechanisms resulting in E-cadherin dysfunction are involved in the tumorigenesis of HDGC. Histopathology exhibits characteristic signet ring cells, and immunohistochemical staining may show negativity for E-cadherin and other signaling proteins. Early HDGC is difficult to detect by endoscopy due to the development of lesions beneath the mucosa. Prophylactic gastrectomy is the most recommended treatment for pathogenic CDH1 variant carriers. Recent studies have promoted the progression of promising molecular-targeted therapies and management strategies. This review summarizes recent advances in CDH1 variant types, tumorigenesis mechanisms, diagnosis, and therapy, as well as clinical implications for future gene therapies.

Synchronous multiple primary gastrointestinal cancers with CDH1 mutations: A case report.

BACKGROUND: Synchronous multiple primary cancers (SMPC) mean two or more malignant tumors occurring simultaneously and with different origins no matter what types they are or where they are located. The carcinogenesis of SMPC often involves variations of some specific genes. However, the correlation between CDH1 mutations and synchronous multiple primary gastrointestinal cancers is largely unknown. CASE SUMMARY: A 62-year-old woman had sustained abdominal pain for one week and visited our hospital. Gastrointestinal endoscopy revealed multiple small polypoid lesions in both the stomach and colorectum. Computed tomography and laboratory results were within normal limits. Pathological evaluation confirmed signet ring cell carcinoma without obvious metastatic evidence. Malignant cells showed negativity for E-cadherin and positivity for ß-catenin in the cytoplasm and nucleus. DNA sequencing performed on paraffin-embedded tissue revealed two exactly coincident alterations in CDH1, C.57T>G and C.1418A>T. CONCLUSION: This case suggests that the combination of CDH1 mutations and WNT/ß-catenin signaling activation contributes to the carcinogenesis of gastrointestinal SMPC.