# Immunoprofiling Reveals GATA3 as a Prognostic Marker in Transformed Mycosis Fungoides

## TL;DR

This study identifies GATA3 as a strong predictor of poor survival in transformed mycosis fungoides, a rare and aggressive skin cancer.

## Contribution

GATA3 is shown to be a novel prognostic marker for risk stratification and potential targeted therapy in TMF.

## Key findings

- High GATA3 expression correlates with significantly worse survival in TMF patients.
- Three distinct immunoprofiles were identified, with high GATA3 linked to the poorest outcomes.
- GATA3 expression indicates a Th2-skewed immunosuppressive tumor environment.

## 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.