Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma

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  • Livasy, Chad
    • Affiliation: School of Medicine, Department of Pathology and Laboratory Medicine, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Karaca, Gamze
    • Affiliation: School of Medicine, Department of Genetics
  • Nanda, Rita
    • Other Affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA
  • Tretiakova, Maria S.
    • Other Affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA
  • Olopade, Olufunmilayo I.
    • Other Affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA
  • Moore, Dominic T.
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Perou, Charles
    • Affiliation: School of Medicine, Department of Pathology and Laboratory Medicine, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
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 less than 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.
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  • Article
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  • In Copyright
Journal title
  • Modern Pathology
Journal volume
  • 19
Journal issue
  • 2
Page start
  • 264
Page end
  • 271
Language
  • English
Version
  • Postprint
ISSN
  • 1530-0285

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