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TFEB rearranged renal cell carcinoma. A clinicopathologic and molecular study of 13 cases. Tumors harboring MALAT1-TFEB, ACTB-TFEB, and the novel NEAT1-TFEB translocations constantly express PDL1
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TFEB rearranged renal cell carcinoma. A clinicopathologic and molecular study of 13 cases. Tumors harboring MALAT1-TFEB, ACTB-TFEB, and the novel NEAT1-TFEB translocations constantly express PDL1
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TFEB rearranged renal cell carcinoma. A clinicopathologic and molecular study of 13 cases. Tumors harboring MALAT1-TFEB, ACTB-TFEB, and the novel NEAT1-TFEB translocations constantly express PDL1
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Journal Article
TFEB rearranged renal cell carcinoma. A clinicopathologic and molecular study of 13 cases. Tumors harboring MALAT1-TFEB, ACTB-TFEB, and the novel NEAT1-TFEB translocations constantly express PDL1
2021
Overview
Renal cell carcinomas with t(6;11) chromosome translocation has been classically characterized by the rearrangement of the TFEB gene, located on chromosome 6, and MALAT1 gene, located on chromosome 11. Recently, a few other genes have been described as fusion partners in TFEB rearranged renal cell carcinomas. Although most of TFEB rearranged renal cell carcinomas have an indolent behavior, in the rare cases of advanced metastatic disease targeted therapy and predictive markers remain lacking. In the present study, we collected 13 TFEB rearranged renal cell carcinomas, confirmed by FISH, analyzing their morphology and exploring the novel gene partners. Looking for predictive markers, we have also performed PDL1 immunohistochemical analysis by using four different assays (E1L3N, 22C3, SP142, and SP263). MALAT1 gene rearrangement has been found in ten tumors, five cases showing classical biphasic morphology with “rosettes”, five cases without “rosettes” mimicking other renal cell carcinomas or epithelioid angiomyolipoma/pure epithelioid PEComa. We identified two different partner genes, ACTB and NEAT1, the latter previously unreported and occurring in a tumor with an unusual solid and cystic appearance. In both cases, the “rosettes” were absent. In one case no gene partner was identified. Overall, in 12 of 13 TFEB-rearranged renal cell carcinomas staining for PDL1 SP263 was observed, whereas the other antibodies were less reliable or more difficult to interpret. In conclusion, we described the third case of ACTB-TFEB rearranged renal cell carcinoma and a novel NEAT1-TFEB rearranged renal cell carcinoma, both without the distinctive biphasic morphology typical of t(6;11) renal cell carcinoma. Finally, PDL1 SP263 was constantly expressed in TFEB rearranged renal cell carcinoma with possible clinical benefit which requires further investigations.
Publisher
Elsevier Inc,Nature Publishing Group US,Elsevier Limited
Subject
/ 14/32
/ 45/23
/ Adult
/ Aged
/ Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics
/ Biomarkers, Tumor - analysis
/ Biomarkers, Tumor - genetics
/ Carcinoma, Renal Cell - genetics
/ Carcinoma, Renal Cell - immunology
/ Carcinoma, Renal Cell - pathology
/ Cytology
/ Female
/ Genes
/ Humans
/ Kidney Neoplasms - immunology
/ Kidney Neoplasms - pathology
/ Male
/ Medicine
/ Mimicry
/ RNA, Long Noncoding - genetics
/ Tumors
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