Anti-TFE3 (aa 166-254) polyclonal antibody

Renal cell carcinoma (RCC) in which clear cells with papillary architecture are present is a difficult diagnostic challenge. The most common type, clear cell RCC, only rarely has papillary architecture. The second most common one, papillary RCC, only rarely contains clear cells. However, two recently described less-common types, clear cell papillary and Xp11 translocation RCC characteristically feature both papillary architecture and cells with clear cytoplasm. Accurate diagnosis has both prognostic and therapeutic implications. This study aims to highlight the helpful cytomorphologic and immunohistochemical features of each of these entities to enable reproducible classification. Sixty RCC cases with clear cells and papillary architecture were selected and classified according to The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia and graded according to The International Society of Urological Pathology (ISUP) grading system for renal cell carcinoma then stained for CK7, carbonic anhydrase IX (CA IX), alpha-methylacyl-CoA-racemase (AMACR) and TFE-3. The characteristic immunoprofile of Clear RCC is CK7-, AMACR-, CA IX+ and TFE3-, papillary RCC is CK7+, AMACR+, CAIX- and TFE3-, while for clear cell papillary RCC it is CK7+, AMACR-, CAIX+ and TFE3- and lastly Xp11translocation RCC is CK7-, AMACR+, CAIX- and TFE3+. Immunohistochemical staining for CA IX, CK7, AMACR and TFE3 comprises a concise panel for distinguishing RCC with papillary and clear pattern.

AimsMITF, TFE3, TFEB and TFEC belong to the same microphthalmia-associated transcription factor family (MiT). Two transcription factors in this family have been identified in two unusual types of renal cell carcinoma (RCC): Xp11 translocation RCC harbouring TFE3 gene fusions and t(6;11) RCC harbouring a MALAT1-TFEB gene fusion. The 2016 World Health Organisation classification of renal neoplasia grouped these two neoplasms together under the category of MiT family translocation RCC. RCCs associated with the other two MiT family members, MITF and TFEC, have rarely been reported. Herein, we identify a case of MITF translocation RCC with the novel PRCC-MITF gene fusion by RNA sequencing. Methods and resultsHistological examination of the present tumour showed typical features of MiT family translocation RCCs, overlapping with Xp11 translocation RCC and t(6;11) RCC. However, this tumour showed negative results in TFE3 and TFEB immunochemistry and split fluorescence in-situ hybridisation (FISH) assays. The other MiT family members, MITF and TFEC, were tested further immunochemically and also showed negative results. RNA sequencing and reverse transcription-polymerase chain reaction confirmed the presence of a PRCC-MITF gene fusion: a fusion of PRCC exon 5 to MITF exon 4. We then developed FISH assays covering MITF break-apart probes and PRCC-MITF fusion probes to detect the MITF gene rearrangement. ConclusionsThis study both proves the recurring existence of MITF translocation RCC and expands the genotype spectrum of MiT family translocation RCCs.