A 55-year-old postmenopausal woman presents with a 2 cm breast mass. Core biopsy shows invasive lobular carcinoma (ILC). The molecular feature that distinguishes ILC from invasive ductal carcinoma at the cellular adhesion level is:

• A Overexpression of N-cadherin causing epithelial-mesenchymal transition (EMT) and loss of cell polarity
• B BRCA2 frameshift mutation disrupting homologous recombination and causing high genomic instability
• C Loss of E-cadherin (CDH1) expression, leading to discohesive single-file (Indian file) infiltrating pattern without tubule formation ✓
• D HER2 amplification with high Ki-67 causing aggressive growth pattern and pleomorphic morphology

Explanation

Invasive lobular carcinoma (ILC) is defined by loss of E-cadherin function, either via CDH1 gene mutation (germline or somatic), methylation silencing, or CDH1 protein loss detectable by IHC. E-cadherin is a transmembrane calcium-dependent adhesion molecule; its loss disrupts the adherens junction complex (beta-catenin, alpha-catenin), resulting in cellular discohesion. This produces the hallmark pathological pattern of ILC: discohesive cells arranged in single-file (Indian file) cords or as isolated cells infiltrating the stroma. ILC typically lacks tubule formation, has low-grade nuclei (classical ILC), and is strongly ER-positive. Pleomorphic variant ILC retains CDH1 loss but has grade 3 nuclei. N-cadherin overexpression is associated with EMT in various carcinomas but not specific to ILC. BRCA2 mutations cause high-grade triple-negative breast cancer. HER2 amplification is associated with IDC, not ILC.

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

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Written and medically reviewed by the StethoPrep medical team.