PMID- 37215783 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230523 IS - 2405-8440 (Print) IS - 2405-8440 (Electronic) IS - 2405-8440 (Linking) VI - 9 IP - 5 DP - 2023 May TI - TFE3 gene rearrangement and protein expression contribute to a poor prognosis of renal cell carcinoma. PG - e16076 LID - 10.1016/j.heliyon.2023.e16076 [doi] LID - e16076 AB - BACKGROUND: TFE3-rearranged renal cell carcinoma (TFE3-rearranged RCC) is a type of kidney cancer with a low incidence, with no consensus about whether it has a worse prognosis than clear cell renal cell carcinoma (ccRCC). This study attempted to elucidate the impact of TFE3-rearranged RCC by analyzing its clinical features and prognosis. METHODS: Patients treated in Sun Yat-sen Memorial Hospital (SYSMH) who were suspected to be diagnosed with TFE3-rearranged RCC were divided into two groups, TFE3-rearranged RCC and ccRCC with positive TFE3 protein expression on immunohistochemistry [TFE3(+) ccRCC], by dual-color, break-apart fluorescence in situ hybridization (FISH). After balancing the baseline characteristics with TFE3(+) ccRCC using the propensity score matching (PSM) method in a ratio of 2, we selected patients diagnosed with ccRCC with negative TFE3 protein expression on immunohistochemistry [TFE3(-) ccRCC]. The impact of TFE3 gene rearrangement and protein expression on renal cell carcinoma was determined by feature comparison with a nonparametric test and survival analysis with the Kaplan‒Meier method. RESULTS: Among 37 patients suspected of having TFE3-rearranged RCC, 13 patients were diagnosed with TFE3-rearranged RCC, and 24 patients had TFE3(+) ccRCC. The recurrence and new metastasis of TFE3-rearranged RCC was relatively common, even if the tumor stage was early at the first diagnosis. Through feature comparison and survival analysis, we found that TFE3-rearranged RCC was quite similar to TFE3(+) ccRCC. Compared with TFE3(-) ccRCC, TFE3(+) ccRCC tended to have a larger tumor diameter (P = 0.011), higher neutrophil/lymphocyte ratio (NLR) (P = 0.017) and metastatic potential (P = 0.022), and worse overall survival (OS) (P = 0.043) and PFS (P = 0.016). The survival analysis showed that TFE3-rearranged RCC had a worse PFS than ccRCC (P = 0.002), and TFE3(+) RCC had a worse PFS than TFE3(-) RCC (P = 0.001). According to the stratification system based on the combination of TFE3 and lymphovascular invasion (LVI), we further found that the prognosis from good to poor was TFE3(-) LVI(-), TFE3(+) LVI(-), TFE3(+) LVI(+) and TFE3(-) LVI(+), with statistically significant differences in both OS (P = 0.001) and PFS (P < 0.001). In addition, we also reported two cases with poor prognosis, of which one was TFE3-rearranged RCC and the other was TFE3(+) ccRCC. CONCLUSIONS: This is a novel finding that both FISH confirmed TFE3 gene rearrangement-mediated TFE3-rearranged RCC and IHC confirmed positive TFE3 protein expression [TFE3(+)] contribute to a poor prognosis in RCC, suggesting more active treatment and careful follow-up for TFE3(+) RCC patients. The combination of TFE3 and LVI may be a new risk stratification system for RCC. CI - (c) 2023 The Authors. FAU - Lin, Junyi AU - Lin J AD - Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China. AD - Department of Urology, Minimally Invasive Surgery Center, Guangdong Key Laboratory of Urology, Guangzhou Urology Research Institute, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China. FAU - Tang, Zhuang AU - Tang Z AD - Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China. AD - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, China. FAU - Zhang, Chengjunyu AU - Zhang C AD - Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China. AD - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, China. FAU - Dong, Wen AU - Dong W AD - Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China. AD - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, China. AD - Guangdong Provincial Clinical Research Center for Urological Diseases, Guangzhou, Guangdong, 510120, China. FAU - Liu, Yeqing AU - Liu Y AD - Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510120, China. FAU - Huang, Hao AU - Huang H AD - Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China. AD - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, China. FAU - Liu, Hao AU - Liu H AD - Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China. AD - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, China. FAU - Huang, Jian AU - Huang J AD - Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China. AD - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, China. AD - Guangdong Provincial Clinical Research Center for Urological Diseases, Guangzhou, Guangdong, 510120, China. FAU - Lin, Tianxin AU - Lin T AD - Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China. AD - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, China. AD - Guangdong Provincial Clinical Research Center for Urological Diseases, Guangzhou, Guangdong, 510120, China. FAU - Chen, Xu AU - Chen X AD - Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China. AD - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, China. AD - Guangdong Provincial Clinical Research Center for Urological Diseases, Guangzhou, Guangdong, 510120, China. LA - eng PT - Journal Article DEP - 20230506 PL - England TA - Heliyon JT - Heliyon JID - 101672560 PMC - PMC10196445 OTO - NOTNLM OT - LVI OT - Prognosis OT - Renal cell carcinoma OT - TFE3 OT - TFE3-Rearranged RCC COIS- The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/05/22 19:11 MHDA- 2023/05/22 19:12 PMCR- 2023/05/06 CRDT- 2023/05/22 12:31 PHST- 2023/01/24 00:00 [received] PHST- 2023/04/30 00:00 [revised] PHST- 2023/05/04 00:00 [accepted] PHST- 2023/05/22 19:12 [medline] PHST- 2023/05/22 19:11 [pubmed] PHST- 2023/05/22 12:31 [entrez] PHST- 2023/05/06 00:00 [pmc-release] AID - S2405-8440(23)03283-8 [pii] AID - e16076 [pii] AID - 10.1016/j.heliyon.2023.e16076 [doi] PST - epublish SO - Heliyon. 2023 May 6;9(5):e16076. doi: 10.1016/j.heliyon.2023.e16076. eCollection 2023 May.