Abstract
Transformed mycosis fungoides (TMF) is a rare, aggressive variant of cutaneous T-cell lymphoma characterized by the presence of large neoplastic cells and poor clinical outcomes. A retrospective cohort of 22 TMF patients was analyzed using immunohistochemistry on formalin-fixed, paraffin-embedded (FFPE) tissue for GATA3 (n = 20), T-bet (n = 22), and STAT3 (n = 22). Expression was quantified by image analysis integrated optical density per total area (IOD/area), standardized by z-score and correlated with survival. Seventeen patients with complete data underwent unsupervised clustering (k-means) and principal component analysis (PCA) based on marker expression profiles. High GATA3 expression was strongly associated with worse prognosis (median OS: 8.6 months vs. 41.7 months, p = 0.00094). T-bet and STAT3 expressions showed no significant individual association with survival. Clustering analysis revealed three distinct immunoprofiles: (1) low expression of all markers (intermediate survival, 28.1 months), (2) high STAT3 and T-bet expressions with intermediate GATA3 expression (longest survival, 53.1 months), and (3) high GATA3 expression with low STAT3 and T-bet expressions (poorest survival, 9.5 months). GATA3 is a robust prognostic marker in TMF, identifying patients with particularly poor outcomes. Its elevated expression delineates a Th2-skewed, immunosuppressive phenotype that may inhibit Th1/Th17 pathways via transcriptional repression. Integrative profiling reveals immunobiological subgroups with divergent prognoses, supporting GATA3 as a potential tool for risk stratification and a candidate for targeted intervention in TMF.