Clinicopathological Analysis of GATA3 Positive Breast Cancers with Molecular Subtypes: A Cross-sectional Study

Abstract

Introduction: In breast carcinoma, a panel of various marker proteins are used to characterise tumour subtypes, confirm tissue of origin, distinguish metastatic tumours from primary tumours, and provide additional information that may be important for prognosis, predicting response to therapy, or evaluating residual tumours post-treatment. Aim: To investigate the immunohistochemical expression of GATA binding protein 3 (GATA3) in breast carcinoma. Materials and Methods: This cross-sectional study was conducted in the Department of Pathology in collaboration with the Department of Surgery at Pt. BD Sharma, PGIMS, Rohtak, Haryana, India over the period of one year from April 2023 to March 2024. Tumour specimens (n=60) were obtained after modified radical mastectomy. All clinicopathological parameters were noted. Histological tumour grading was performed using the Nottingham Modification of the Bloom-Richardson (MBR) grading system, and representative sections were subjected to immunohistochemical analysis for Oestrogen Receptor (ER), Progesterone Receptor (PR), Human Epidermal growth factor Receptor 2/Neu (HER2/Neu), and Ki-67 for molecular subtyping, as well as GATA3 expression. The association between GATA3 expression and clinicopathological parameters and different breast cancer molecular subtypes was calculated using the Chi-square and Fisher’s exact Test. The collected data were analysed using the software package Statistical Package for the Social Sciences (SPSS) version 24.0. Results: The age of patients ranged from 28 to 75 years, with a median age of 50.0 years. Triple-negative/basal-like was the most common molecular subtype 20 (33.33%) among all cases. Sixteen cases (26.67%) were of the luminal A subtype. Other molecular subtypes included 12 cases (20%) each of luminal B and HER2-enriched types. GATA3 was positive in 45 of 60 cases, constituting 75% of all cases. A statistically significant relationship was observed between GATA3-positive tumours and histological grade (p-value=0.024), ER status (p-value<0.001), PR status of the tumour (p-value=0.001), and the luminal A and B molecular subtypes (p-value<0.001). No association was found between GATA3 expression and patient age, side of the breast involved, tumour size, histologic subtype, lymph node status, Nottingham Prognostic Index (NPI), or HER2/Neu status of the tumour. Conclusion: GATA3 is a sensitive marker of breast carcinoma and exhibits nuclear expression that aids in better interpretation. It can be especially useful in metastatic breast carcinoma when considered in conjunction with other immunohistochemical markers. GATA3-positive breast cancers demonstrate luminal differentiation and are characterised by high ER and PR expression.