TFE3 immunohistochemistry in renal cell carcinomas: does the clone really matter?

R enal cell carcinomas (RCC) constitute 80-85% of malignant tumours of the kidney.There are many subtypes defined so far, and new entities are being defined as pathological and molecular analyses increase [1].MiT (microphthalmia-associated transcriptional factor) family translocation carcinomas are rare and account for 1-4% of renal tumors in adults and ap-proximately half of the RCCs in children [2].These tumours are characterized by fusions involving TFE3 or TFEB genes and were included as two subcategories in the 2016 WHO classification.However, with the 5 th edition of the WHO Classification of Urinary and Male Genital Tumours (2022), these two entities were classified separately as TFE3-rearranged RCC (TFE3-ABSTRACT OBJECTIVE: TFE3 rearranged carcinomas constitute 5% of malignant tumours of the kidney in adults.TFE3 immunohistochemistry plays a crucial role in the diagnosis.TFE3 positivity in the appropriate histological context supports the diagnosis of Xp11 translocation renal cell carcinomas.However, there isn't any standardized approach to performing and interpreting immunohistochemical staining.METHODS: A total of 51 renal cell carcinomas are included in the study.In this study, we compared the expression profiles of two different anti-TFE3 antibody clones (MRQ37, Cell Marque, and IHC627, GeneAbTM) on renal cell carcinoma samples that have conflicting morphologies and assessed the overall performance of these clones to identify TFE3 rearranged carcinomas. RESULTS:There was a statistically significant difference in terms of immunohistochemical staining with TFE3-MRQ37 clone between TFE3 rearranged renal cell carcinomas and other subtypes, while no significant difference was found in staining with TFE3-IHC672.47% of cases were stained with the TFE3-IHC672 clone and 9.8 % of cases were stained with the TFE3-MRQ37 clone at different staining intensities and proportions.CONCLUSION: The TFE3-MRQ37 clone is easier to interpret because of the absence of background staining and is more reliable in identifying TFE3 rearranged renal cell carcinomas.However, because of various sensitivity and specificity rates, and immunoreactivity in many subtypes of renal cell carcinomas, there is a need for a standardised approach for TFE3 immunohistochemistry for diagnostic use in TFE3-tRCCs.