Immunohistochemical analysis of clinicopathological predictors for BRCA1 protein alterations in invasive breast carcinoma; a cross-sectional study

Abstract

Introduction: Breast cancer is a heterogeneous disease influenced by genetic, hormonal, and molecular factors. Among these, BReast CAncer gene 1 (BRCA1) protein alterations play a critical role in hereditary breast cancers and may also have implications in sporadic cases.

Objectives: This study aims to analyze the immunohistochemical expression of BRCA1 protein and its association with clinicopathological predictors. Materials and Methods: This cross-sectional study analyzed 100 paraffin-embedded tissue blocks from female breast cancer patients treated at educational and therapeutic hospitals in Isfahan, Iran, between March 2018 and April 2023. Tissue sections underwent immunohistochemical staining to evaluate BRCA1 protein expression. Patient data, including demographic information (age and family history of breast cancer), tumor characteristics (size, grade, and lymph node involvement), hormonal receptor status (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [HER2]) and Ki67 expression were extracted from archived medical records and staining results. Statistical tests were used to assess the correlation between clinicopathological factors and BRCA1 alteration status.

Results: This study identified several clinico-pathological factors significantly associated with BRCA1 alteration status. Advanced tumor grades and lymph node involvement were strongly linked to BRCA1 mutations, with grade II and III tumors showing substantial increases in likelihood compared to grade I. Initially, hormone
receptor-negative status also correlated with altered BRCA1. However, after adjusting for confounders, only tumor grade and lymph node involvement remained as independent predictors. Specifically, grade II and III tumors demonstrated significantly elevated odds, while lymph node involvement showed a strong association. Although negative ER still showed an increased likelihood, it did not reach statistical significance in the adjusted analysis, and neither PR nor HER2 status retained predictive value.

Conclusion: The study findings suggest strong relationships between BRCA1 alterations and advanced disease characteristics, particularly the nodal metastasis, hormone receptor negativity, and higher tumor grade. The magnitude of association for tumor grade and nodal metastasis progression highlights their potential clinical relevance in BRCA1-related oncogenesis as independent predictors.