Clinical, diagnostic and prognostic relevance of GATA3 in malignant pleural mesothelioma: a retrospective cohort study

Malignant pleural mesothelioma (MPM) is an aggressive malignancy with a poor prognosis and limited treatment options. Recently, GATA3 has emerged as a useful adjunct immunohistochemical marker, especially for non-epithelioid subtypes. Although the diagnostic and prognostic roles of GATA3 have been described in other malignancies, its frequency and clinical relevance in MPM remains unclear. We conducted a retrospective, single-center cohort study of 91 patients with histologically confirmed MPM and suitable tumor tissue for GATA3 immunohistochemistry. Staining intensity was scored semi-quantitatively (mild, moderate, or strong). Clinical, pathological, and treatment data were collected. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier methods and Cox regression models. GATA3 expression was observed in 64 of 91 cases (70.3%). No differences in PFS or OS were observed according to GATA3 positivity. GATA3 positivity demonstrated the ability to discrimine MPM and LUAD, with area under the curve (AUC) values of 0.83 for overall MPM, 0.81 for epithelioid MPM, and 0.93 for non-epithelioid MPM. The diagnostic performance was further improved by Combining GATA3 with WT1, yielding AUC values of 0.94 for MPM, 0.93 for epithelioid MPM, and 1.00 for non-epithelioid MPM. High GATA3 staining intensity was associated with shorter median PFS (6.14 vs. 10.94 months; p = 0.023) and OS (7.89 vs. 33.35 months; p = 0.004) compared with cases showing low or moderate intensity. High GATA3 staining intensity remained an independent adverse prognostic factor for OS (HR 6.59; 95% CI 1.55–28.05; p = 0.011) in a multivariate analysis adjusted for asbestos exposure, ECOG PS, clinical stage, PD-L1 positivity, and histological type. GATA3 is frequently expressed in MPM and demonstrates good diagnostic performance differentiating MPM from LUAD. Furthermore, high GATA3 staining intensity was independently associated with a poorer prognosis. These findings support GATA3 diagnostic utility and suggest a potential prognostic role in MPM that warrants validation in larger, prospective cohorts.