A 52-year-old woman undergoes mastectomy for invasive lobular carcinoma. Compared to invasive ductal carcinoma (IDC NST), lobular carcinoma has a distinct growth pattern of single-file infiltrating cells. The molecular basis for this distinctive infiltrative pattern is:
- A Gain-of-function ERBB2 (HER2) amplification causing increased cell motility
- B BRCA1 mutation promoting epithelial-mesenchymal transition
- C Loss of E-cadherin (CDH1) expression due to CDH1 gene mutation or silencing, disrupting cell-cell adhesion ✓
- D PI3K/AKT pathway activation causing loss of cell polarity
Explanation
The classic Indian-file (single-file, targetoid) infiltrating pattern of invasive lobular carcinoma (ILC) results from loss of E-cadherin, a transmembrane epithelial adhesion molecule encoded by CDH1. E-cadherin loss (via mutation, LOH, or promoter methylation) eliminates cell-cell adhesion, allowing individual tumor cells to infiltrate independently without forming cohesive glands or nests. CDH1 mutations are somatic in most ILC and germline in hereditary diffuse gastric cancer/lobular breast cancer syndrome. IHC for E-cadherin (negative in ILC, positive in IDC) is diagnostically useful.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.