Renal Translocation Carcinomas

Abstract

We report clinicopathologic features of a large series of renal translocation carcinomas from a multicentric study. Diagnosis was performed by cytogenetic examination of fresh material and/or by immunochemistry with antibodies directed against the C-terminal part of transcription factor E3 (TFE3) and native transcription factor EB (TFEB) proteins. Clinical data, follow-up, and histologic features were assessed. Antibodies against CK7, CD10, vimentin, epithelial membrane antigen, AE1-AE3, E-cadherin, alpha-methylacyl-coenzyme A racemase, melan A, and HMB45 were tested on tissue microarrays. Whole-genome microarray expression profiling was performed on 4 tumors. Twenty-nine cases were diagnosed as TFE3 and 2 as TFEB renal translocation carcinomas, including 13 males and 18 females, mean age 24.6 years. Two patients had a previous history of chemotherapy and 1 had a history of renal failure. Mean size of the tumor was 6.9 cm. Thirteen cases were > or = pT3 stage. Twelve cases were N+ or M+. Mean follow-up was 29.5 months. Three patients presented metastases and 5 have died. Mixed papillary and nested patterns with clear and/or eosinophilic cells represented the most consistent histologic appearance, with common foci of calcifications regardless of the type of translocation. Using a 30 mn incubation at room temperature, TFE3 immunostainings were positive in only 82% of our TFE3 translocation carcinomas. Both TFE3 and TFEB renal translocation carcinomas expressed CD10 and alpha-methylacyl-coenzyme A racemase in all cases. An expression of E-cadherin was observed in two-third of cases. Cytokeratins were expressed in less than one-third of cases. Melanocytic markers were expressed at least weakly in all cases except two. Unsupervised clustering on the basis of the gene expression profiling indicated a distinct subgroup of tumors. TRIM 63 glutathione S-transferase A1 and alanyl aminopeptidase are the main differentially expressed genes for this group of tumors. Our results suggest that these differentially expressed genes may serve as novel diagnostic or prognostic markers.

Cytologic Features of Renal Carcinoma Associated with Xp11.2 Translocations/TFE3 Gene Fusions: A Case Report with Voided and Catheterized Urine Cytology and a Literature Review

“…Chromophobe RCCs are positive for epithelial membrane antigen and pan-CK and negative for vimentin, and collecting duct carcinomas are typically positive for Ulex europaeus agglutinin 1 and vimentin [12]. The distinction of Xp11.2 RCCs from eAMLs can be problematic: both tumors are typically negative for epithelial markers, and a subset of Xp11.2 RCCs may be positive for melanocytic markers such as human melanin black-45 and MART-1/melan A [13]. In such cases, immunostaining with α-smooth muscle actin is useful for differentiation, as it is only positive in eAMLs [3].…”

Next-Generation Sequencing of Translocation Renal Cell Carcinoma Reveals Novel RNA Splicing Partners and Frequent Mutations of Chromatin-Remodeling Genes

“…Although in a previous study tumors of the MITF/TFE family were shown to display a unique gene expression signature (19), their full transcriptomic remains unknown.…”

MiT translocation renal cell carcinomas: two subgroups of tumours with translocations involving 6p21 [t (6; 11)] and Xp11.2 [t (X;1 or X or 17)]

“…This tumour harbours translocations involving the transcription factor EB (TFEB) and Alpha (the latter also known as MALATI ). Genetically, TFEB RCC has been characterized by the fusion of the 5’ portion of Alpha , also known as MALATI (Genbank accession number AF203815), an intronless gene mapped at 11q12, with TFEB at 6p21 Inamura et al 2012; Rao et al 2012 with fewer than 30 cases reported to date Hora et al 2009; Inamura et al 2012; Rao et al 2012; Camparo et al 2008; Suarez-Vilela et al 2011. First 11 cases were reviewed by Hora et al 2009, cases published since 2007 are summarised in Table 1.…”