Molecular Subtyping of Triple Negative Breast Cancer by Surrogate Immunohistochemistry Markers

Triple negative breast cancer (TNBC) is a heterogeneous disease and an attempt was made to classify TNBCs into surrogate molecular subtypes using immunohistochemical markers. Tissue microarrays were constructed for 245 cases of TNBCs. For classification of TNBCs immunohistochemistry was done on tissue microarrays for cytokeratin 5/6, 4/14 (CK5/6, CK4/14), epidermal growth factor receptor (EGFR), vimentin, E-cadherin, claudin 3 and 7, androgen receptor (AR) and aldehyde dehydrogenase1A. The TNBCs were classified into basal-like 1 (BL1) type (CK5/6+, CK4/14+, EGFR- n=32; 13.1%), basal-like 2 (BL2) type (EGFR+, n=4; 1.6%), mesenchymal type (Vimentin+, E-cadherin ̅, claudin 3-and 7-, n=70; 28.6%), luminal androgen type (AR+, n=41; 16.7%), mixed type (n=37; 15.1%), and unclassified type (n=61; 24.9%). Luminal androgen receptor subtype showed apocrine features, and was associated with older age group, lower proliferation index and high frequency of lymph node metastasis. Basal subtype was cellular with rich stromal lymphocytic infiltrate. Mesenchymal stem like subtype was associated with younger age group with metaplastic and mesenchymal features. Mesenchymal stem like and unclassified subtype had shorter overall survival with median of 68.2 and 69.2 months, respectively, and the BL2 had median disease-free survival of 35.4 months. On immunohistochemistry TNBC is a heterogeneous entity composed of 6 major subtypes. Immunohistochemical subtyping of TNBC can provide information on prognostication and selection of appropriate targeted therapy for these patients.