Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma.
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.
Livasy
Chad A
CA
Department of Pathology and Lab Medicine, University of North Carolina, Chapel Hill, NC 27599-7525, USA. cal@med.unc.edu
Karaca
Gamze
G
Nanda
Rita
R
Tretiakova
Maria S
MS
Olopade
Olufunmilayo I
OI
Moore
Dominic T
DT
Perou
Charles M
CM
D000199:Actins / Q000032:analysis; D001940:Breast / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D053555:Keratin-5; D053553:Keratin-6; D007633:Keratins / Q000032:analysis; D009130:Muscle, Smooth / Q000737:chemistry; D009361:Neoplasm Invasiveness; D015260:Neprilysin / Q000032:analysis; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D010750:Phosphoproteins / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis / Q000235:genetics; D015534:Trans-Activators / Q000032:analysis; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014746:Vimentin / Q000032:analysis
D000199:Actins; D004268:DNA-Binding Proteins; D066246:ErbB Receptors; D053555:Keratin-5; D053553:Keratin-6; D007633:Keratins; D015260:Neprilysin; D010750:Phosphoproteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014746:Vimentin; C503940:KRT5 protein, human; C507569:KRT6A protein, human; C507570:KRT6B protein, human; C507571:KRT6C protein, human; C115051:TP63 protein, human