Immunohistochemistry-based molecular subtyping of triple-negative breast cancer and its prognostic significance

Abstract

Background: Immunohistochemistry (IHC)-based protein markers representing molecular subtypes are of great value for routine use. This study aimed to evaluate the frequency distributions of the molecular subtypes of triple-negative breast cancer (TNBC) using IHC-based surrogate markers and examined their prognostic value. Methods: Patients with TNBC treated at a university hospital in Southern Thailand were included in this study. Expression levels of androgen receptor, CD8, Forkhead box transcription factor C1, and Doublecortin-like kinase 1 were detected in tumor tissue to classify them into luminal androgen receptor (LAR), immunomodulatory (IM), basal-like immunosuppressed (BLIS), mesenchymal-like (MES), and unclassifiable (UC) subtypes. The association between variables and disease-free survival (DFS) and overall survival (OS) was analyzed using Cox proportional hazards regression. Results: Among the 195 cases of TNBC, the frequency distribution of the IHC-based subtype was as follows: BLIS, 52.8%; LAR, 19.0%; IM, 17.4%; MES, 0.5%; and un-classifiable, 10.3%. BLIS subtype was significantly found in younger ages (mean: 49.6 years) than other subtypes (mean: 51-57.7 years). LAR and BLIS subtypes were significantly associated with poorer OS compared to the IM subtype in univariate analysis, however, only BLIS was significant in multivariate analysis (HR: 3.29, 95% CI: 1.01-10.72). IHC-based subtype was not found to be associated with DFS. Conclusion: This study revealed the differences in the proportion frequency of IHC-based TNBC subtypes in Thai patients compared to other populations. IHC-based molecular subtyping may be beneficial for prognosis. However further refinement of the molecular classification of TNBC is needed for better clinical relevance.

Keywords: breast cancer; immunohistochemistry; molecular subtype; prognosis; triple-negative breast cancer.