Feasibility of Classification of Triple Negative Breast Cancer by Immunohistochemical Surrogate Markers

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Using the 7 immunohistochemical surrogate markers, we tried to classify 200 TNBCs into 4 molecular subtypes; luminal androgen receptor, mesenchymal, basal-like immune-activated, and basal-like immune-suppressive types. Our results showed that each subtype had significant differences in clinicopathological characteristics and prognosis. Introduction: Recently, Burstein et al identified 4 stable molecular subtypes of triple negative breast cancer (TNBC) by mRNA profiling: luminal androgen receptor (LAR), mesenchymal (MES), basal-like immune-activated (BLIA), and basal-like immune-suppressive (BLIS) types. The purpose of this study was to assess the feasibility of immunohistochemistry (IHC) surrogate panel in classifying the TNBC molecular subtypes using a large cohort of TNBC retrieved from a single institution. Materials and Methods: IHC for androgen receptor [AR], claudin-3, E-cadherin, cytokeratin 5/6 [CK5/6], epidermal growth factor receptor [EGFR], indoleamine 2,3-dioxygenase 1 [IDO1], and Forkhead box C1 [FOXC1] were performed using the tissue microarray constructed from 200 TNBC samples. Results: The 200 TNBCs were classified as LAR (AR + , n = 22; 11.0%), MES (claudin 3 and/or E-cadherin , n = 23; 11.5%), basal-like (CK5/6 + and/or EGFR + , n = 85; 42.5%), mixed (n = 60; 30%), and unclassifiable type (n = 10; 5%). LAR type was associated with older patient age, apocrine histologic features, low density of stromal tumor-infiltrating lymphocytes (TIL), and low Ki-67 labeling index. MES type was associated with tumor cell discohesiveness and metaplastic features. Basal-like type was associated with younger patient age, high histologic grade, high stromal TIL density, and high Ki-67 labeling index. Basal-like TNBCs were further classified as BLIA (IDO1 + and FOXC1 , n = 27) or BLIS type (IDO1 - and FOXC1 + , n = 11). BLIS type was associated with large tumor size and low stromal TIL density, which had the worst prognostic outcome among 4 subtypes. Conclusion: The IHC surrogate panel may define TNBC subtypes with distinct clinicopathologic characteristics and prognostic significance.

Original languageEnglish
Pages (from-to)e1123-e1132
JournalClinical Breast Cancer
Issue number5
StatePublished - Oct 2018

Bibliographical note

Publisher Copyright:
© 2018 Elsevier Inc.


  • Basal-like immune-activated
  • Basal-like immune-suppressed
  • Immunohistochemistry
  • Molecular subtype
  • Triple negative breast carcinoma


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