Molecular subtyping and target identification in triple negative breast cancer through immunohistochemistry biomarkers

Abstract

BACKGROUND: The Triple-Negative Breast Cancer (TNBC) molecular subtyping and target identification based on Immunohistochemistry (IHC) is of considerable worth for routine use. Yet, literature on this topic is limited worldwide and needs to be enriched with data from different populations. METHODS: We assessed the IHC expression of subtyping biomarkers (Cytokeratins 5, 14 and 17, Epidermal Growth Factor Receptor, Claudins 3 and 7, E-cadherin, Vimentin and Androgen receptor) and predictive biomarkers (Tumor-infiltrating lymphocytes (TILs) density, Breast Cancer Antigen 1 (BRCA1) and P53) in a cohort of TNBC patients. Clinicopathologic parameters and overall survival (OS) were investigated as well. RESULTS: The patients were aged 50.11 ± 12.13y (more than 40y in 76.56% of patients), and 23.44% had a BC family history. They were in a non-advanced stage: 51.6% T2 stage, 56.2% negative lymph node involvement, 76.6% without metastasis and 64.1% grade II Scarff-Bloom-Richardson classification (SBR). The IHC subtypes were: 53.1% Basal-like1 (BL1), 6.3% Basal-like2 (BL2), 17.2% Mesenchymal (MES), 9.4% Luminal Androgen Receptor (LAR), 4.7% Mixed subtype and 9.4% "Unclassified" type. The LAR subtype involved the youngest patients (40.17 ± 8.68y, p = 0.02). The "Unclassified" subtype expressed the p53 mutated-type pattern more frequently (100%, p = 0.07). The BRCA1 mutated pattern and TILs infiltration were present in (23.44% and 37.5% of patients, respectively). The OS of the subtypes differed significantly (p = 0.007, log-rank test). The subtypes median OS were, respectively, 15.47 mo. (Unclassified), 18.94 mo. (BL2), 27.23 mo. (MES), 27.28 mo. (Mixed), 30.88 mo. (BL1), and 45.07 mo. (LAR). There was no difference in the OS following age, BRCA1 expression, p53 pattern and TILs density. Though, the OS following the TNM stage was different (p = 0.001). A multivariable Cox proportional hazards regression analysis showed that TNM staging and TNBC subtypes, independently influence the OS (p < 0.001 and p = 0.017, respectively). Hence, IHC is useful in TNBC subtyping for prognostic purposes and in the identification of therapeutic biomarkers. Further investigation is required to confirm our results and to implement IHC as a routine tool to improve patient's care.