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Histopathology. 2018 Nov;73(5):758-766. doi: 10.1111/his.13700. Epub 2018 Sep 12.

TFE3 translocation and protein expression in renal cell carcinoma are correlated with poor prognosis.

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Department of Pathology, School of Medicine, Pusan National University, Yangsan, Korea.
The Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, YangSan, Korea.
Department of Pathology, School of Medicine, Dong-A University, Busan, Korea.
Department of Urology, School of Medicine, Pusan National University, Yangsan, Korea.



Since Xp11.2 translocation-associated renal cell carcinoma (TRCC) was first recognised, its morphological features and the clinical significance of TFE3 expression, frequency of gene translocation and diagnostic criteria have been the subject of limited studies. The present retrospective analysis aimed to evaluate the correlation between TFE3 immunoreactivity and its gene translocation status using fluorescence in-situ hybridisation (FISH) and determine how TFE3 translocation and expression affect patient prognosis differently.


We enrolled 303 consecutive renal cell carcinoma cases. Immunohistochemical staining for TFE3 was performed in 303 cases, and FISH analysis was performed for molecular testing. The TCGA data set of renal cell carcinoma was evaluated to validate TFE3 expression and survival analysis. TFE3 expression was associated significantly with the nested alveolar pattern, papillary pattern, eosinophilic cytoplasm, voluminous expansile cytoplasm, nuclear grade, tumour necrosis, sarcomatoid pattern and picket fence appearance. FISH analysis showed break-apart signals in 26 of 32 (81.25%) cases expressing strong or moderate nuclear TFE3 immunoreactivity. Thirteen of 56 samples that showed no or weak TFE3 expression with morphologically suspicious cases were translocation-positive in the FISH assay. The TFE3-translocation group (harbouring TFE3 translocation regardless of TFE3 expression) showed the poorest progression-free survival (PFS), and the TFE3-expressing group (expressing TFE3 but negative for translocation) was correlated significantly with decreased PFS.


Increased TFE3 expression in RCC was associated with poor PFS regardless of the gene translocation status. Moreover, morphological analysis should help to select candidates who would benefit from TFE3 staining and FISH analysis.


FISH ; TFE3; immunohistochemistry; prognosis; renal cell carcinoma

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