Histopathology-Based Molecular Subtyping and Immune Microenvi-ronment Heterogeneity in Invasive Breast Carcinoma

Abstract

This study examined the relationship between immunohistochemistry-defined molecular subtypes of breast carcinoma and the tumour immune microenvironment. A total of 500 invasive breast carcinoma cases were retrospectively analysed using routine histopathology and immunohistochemistry. Tumours were classified into luminal A, luminal B, HER2-enriched, basal-like, and unclassified subtypes based on surrogate markers. Immune cell infiltration was assessed using CD8 and CD68 immunohisto-chemistry in a subset of cases, and immune-related gene expression was analysed by quantitative real-time PCR in selected CD8-dominant and CD68-dominant tumours. Basal-like tumours showed higher CD8 infiltration, while unclassified triple-negative tumours more frequently demonstrated macrophage-dominant immune profiles. Gene expression analysis showed higher expression of cytotoxic and T-cell–associated genes in CD8-dominant tumours compared with CD68-dominant tumours. These findings highlight immune heterogeneity across breast cancer subtypes and support the value of combining routine immunohistochemistry with targeted molecular analysis of invasive breast cancer