A 40-year-old woman with BRCA2 germline mutation is diagnosed with triple-negative breast cancer (ER-/PR-/HER2-). On molecular subtyping (PAM50), the tumour is classified as 'basal-like'. Which IHC marker panel best identifies the basal-like subtype?
- A E-cadherin negative and vimentin positive — indicating epithelial-mesenchymal transition in the claudin-low subtype
- B AR positive and GCDFP-15 positive — defining the molecular apocrine/LAR subtype of TNBC
- C FGFR2 amplification and PTEN loss — immunohistochemically detectable basal-like markers
- D CK5/6 positive and/or EGFR positive in a ER-/PR-/HER2- background — these markers define the basal-like phenotype within TNBC ✓
Explanation
Within the triple-negative breast cancer (TNBC) group, the basal-like subtype is immunohistochemically defined by co-positivity for CK5/6 and/or EGFR expression in the ER-/PR-/HER2- context — termed the 'core basal phenotype' (CBP). These tumors have a gene expression profile resembling normal basal/myoepithelial cells. Basal-like TNBC is enriched for BRCA1/2 mutations, shows high genomic instability, and may respond to PARP inhibitors and platinum chemotherapy. E-cadherin loss + vimentin gain characterises the claudin-low subtype (another intrinsic subtype). AR+ GCDFP-15+ defines the luminal androgen receptor (LAR) subtype of TNBC, which may respond to AR inhibition. FGFR2/PTEN are molecular alterations not directly detected by standard IHC.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.