Diffuse-type gastric adenocarcinoma characteristically infiltrates the gastric wall as scattered single cells and small clusters without forming glands. The molecular alteration most directly responsible for this discohesive growth pattern is:
- A Amplification of ERBB2 (HER2)
- B Mutation of KRAS codon 12
- C Loss of E-cadherin (CDH1) expression ✓
- D Overexpression of matrix metalloproteinases
Correct answer: C. Loss of E-cadherin (CDH1) expression
Explanation
E-cadherin mediates calcium-dependent intercellular adhesion between epithelial cells. Germline CDH1 mutations cause hereditary diffuse gastric cancer, and somatic loss of E-cadherin produces the signet ring cell, discohesive morphology of sporadic diffuse gastric carcinoma. Loss of E-cadherin also underlies lobular carcinoma of the breast. HER2 amplification is seen in intestinal-type gastric cancer, and KRAS mutations do not determine the diffuse growth pattern.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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