Prognostic implications and diagnostic significance of TFE3 rearrangement in renal cell carcinoma

Objectives To investigate the impact of TFE3 rearrangement, analyzing clinicopathological features that influence renal cell carcinoma (RCC) recurrence, and clarify the role of immunohistochemistry (IHC) staining in diagnosis. Methods We screened patients diagnosed of clear cell RCC (ccRCC), fluorescence in situ hybridization (FISH) was performed on all TFE3 positive IHC tumors. Clinicopathological and survival features were collected for analysis. Results Out of 695 patients treated for renal tumors, 478 (68.7%) were ccRCC and 22 were suspected of TFE3 rearrangement based on IHC. Subsequent testing revealed 8 (1.15%) were positive in the FISH test (TFE3-rearranged-RCC) and 14 (2.01%) tested negative. No significant differences were noted in general characteristics among the three groups, except for age, TFE3-rearranged-RCC were younger than ccRCC (median age, 49 vs. 58 years, p=0.02). TFE3-rearranged-RCC exhibited a significant higher recurrence rate compared to ccRCC (50% vs 18.8%) and multivariate analysis revealed that TFE3 rearrangement, along with tumor size and metastasis, was an independent prognostic factor for recurrence (HR=4.6; 95% CI 1.1-21.2; p=0.05). Survival analysis demonstrated a significant shorter PFS (progression-free survival) for TFE3-rearranged-RCC compared to ccRCC. Conclusions TFE3 rearrangement is an independent prognostic factor for recurrence and contributes to a worse PFS, suggesting the necessity of careful follow-up. Diagnosis should be confirmed using FISH due to low specificity of IHC. Further studies are needed to confirm TFE3 IHC staining as a prognostic factor.