Diffuse-type gastric adenocarcinoma is characterized by infiltrating sheets of signet-ring cells with loss of cellular cohesion and extensive peritoneal spread. The molecular alteration most directly responsible for the discohesion in this subtype is:

• A Amplification of the ERBB2 (HER2) gene
• B Activation of the WNT pathway through APC loss
• C Loss of SMAD4 expression
• D Mutation of the CDH1 gene encoding E-cadherin ✓

Explanation

Diffuse gastric carcinoma arises from germline or somatic CDH1 mutations that eliminate E-cadherin, the calcium-dependent adhesion molecule holding epithelial cells together. Loss of intercellular adhesion permits the single-file infiltration of signet-ring cells and early transcoelomic metastasis. HER2 amplification defines the intestinal type and guides trastuzumab therapy, SMAD4 loss is linked to pancreatic carcinoma, and APC loss drives colorectal tumorigenesis through WNT signaling.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.