Phenotypic Evaluation of the Basal-Like Subtype of Invasive Breast Carcinoma

Mod Pathol. 2006 Feb;19(2):264-71. doi: 10.1038/modpathol.3800528.

Abstract

Microarray profiling of invasive breast carcinomas has identified five distinct subtypes of tumors (luminal A, luminal B, normal breast-like, HER2 overexpressing, and basal-like) that are associated with different clinical outcomes. The basal-like subtype is associated with poor clinical outcomes and is the subtype observed in BRCA1-related breast cancers. The aim of this study was to characterize the histologic and immunophenotypic properties of breast basal-like carcinomas that were first positively identified using DNA microarray analysis. Detailed histologic review was performed on 56 tumors with known microarray profiles (23 basal-like, 23 luminal, and 12 HER2+). Immunohistochemistry for estrogen receptor (ER), HER2, EGFR, smooth muscle actin (SMA), p63, CD10, cytokeratin 5/6, cytokeratin 8/18, and vimentin was performed on 18 basal-like, 16 luminal, and 12 HER2+ tumors. The basal-like tumors were grade 3 ductal/NOS (21/23) or metaplastic (2/23) carcinomas that frequently showed geographic necrosis (17/23), a pushing border of invasion (14/23), and a stromal lymphocytic response (13/23). Most basal-like tumors showed immunoreactivity for vimentin (17/18), luminal cytokeratin 8/18 (15/18), EGFR (13/18), and cytokeratin 5/6 (11/18), while positivity for the myoepithelial markers SMA (4/18), p63 (4/18) and CD10 (2/18) was infrequent. All basal-like tumors tested were ER- and HER2-. Morphologic features significantly associated with the basal-like subtype included markedly elevated mitotic count (P<0.0001), geographic tumor necrosis (P=0.0003), pushing margin of invasion (P=0.0001), and stromal lymphocytic response (P=0.01). The most consistent immunophenotype seen in the basal-like tumors was negativity for ER and HER2, and positivity for vimentin, EGFR, cytokeratin 8/18, and cytokeratin 5/6. The infrequent expression of myoepithelial markers in basal-like carcinomas does not support a direct myoepithelial cell derivation of these tumors. These findings should further assist in the identification of basal-like carcinomas in clinical specimens, facilitating treatment and epidemiologic studies of this tumor subtype.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / analysis
  • Breast / chemistry
  • Breast / metabolism
  • Breast / pathology*
  • Breast Neoplasms / classification*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • DNA-Binding Proteins
  • ErbB Receptors / analysis
  • Female
  • Gene Expression Profiling
  • Genes, Tumor Suppressor
  • Humans
  • Immunohistochemistry
  • Keratin-5
  • Keratin-6
  • Keratins / analysis
  • Muscle, Smooth / chemistry
  • Neoplasm Invasiveness
  • Neprilysin / analysis
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Phosphoproteins / analysis
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-2 / genetics
  • Receptors, Estrogen / analysis
  • Receptors, Estrogen / genetics
  • Trans-Activators / analysis
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Vimentin / analysis

Substances

  • Actins
  • DNA-Binding Proteins
  • KRT5 protein, human
  • KRT6A protein, human
  • KRT6B protein, human
  • KRT6C protein, human
  • Keratin-5
  • Keratin-6
  • Phosphoproteins
  • Receptors, Estrogen
  • TP63 protein, human
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Vimentin
  • Keratins
  • ErbB Receptors
  • Receptor, ErbB-2
  • Neprilysin