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TFE 3 translocation and protein expression in renal cell carcinoma are correlated with poor prognosis
Author(s) -
Lee Hyun Jung,
Shin Dong Hoon,
Kim So Young,
Hwang Chung Su,
Lee Jung Hee,
Park Won Young,
Choi Kyung Un,
Kim Jee Yeon,
Lee Chang Hun,
Sol Mee Young,
Rha Seo Hee,
Park Sung Woo
Publication year - 2018
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13700
Subject(s) - chromosomal translocation , immunohistochemistry , tfe3 , renal cell carcinoma , staining , cytoplasm , pathology , biology , carcinoma , gene expression , gene , microbiology and biotechnology , cancer research , medicine , genetics , promoter
Aims Since Xp11.2 translocation‐associated renal cell carcinoma ( TRCC ) was first recognised, its morphological features and the clinical significance of TFE 3 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 TFE 3 immunoreactivity and its gene translocation status using fluorescence in‐situ hybridisation ( FISH ) and determine how TFE 3 translocation and expression affect patient prognosis differently. Methods and results We enrolled 303 consecutive renal cell carcinoma cases. Immunohistochemical staining for TFE 3 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 TFE 3 expression and survival analysis. TFE 3 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 TFE 3 immunoreactivity. Thirteen of 56 samples that showed no or weak TFE 3 expression with morphologically suspicious cases were translocation‐positive in the FISH assay. The TFE 3 ‐translocation group (harbouring TFE 3 translocation regardless of TFE 3 expression) showed the poorest progression‐free survival ( PFS ), and the TFE 3‐expressing group (expressing TFE 3 but negative for translocation) was correlated significantly with decreased PFS . Conclusion Increased TFE 3 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 TFE 3 staining and FISH analysis.