Altered transcription factor E3 expression in unclassified adult renal cell carcinoma indicates adverse pathological features and poor outcome

Mir, Maria Carmen; Trilla, Enrique; Torres, Inés M. de; Panizo, Ángel; Zlotta, Alexander; Rhijn, Bas van; Moróte, Juan

doi:10.1111/j.1464-410x.2010.09818.x

Cited by 34 publications

(25 citation statements)

References 19 publications

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“…In our study, in all patients the diagnosis was made at a younger age (mean 28 years old). Series have reported mean tumor size ranging from 6.8 to 9.2 cm in the largest diameter, which is larger than the 5.8 cm in our series [4,23,25].…”

Section: Discussioncontrasting

confidence: 56%

“…The grading system is determined on nuclear characteristics and has been proven to be a powerful prognostic predictor for RCC [43–45]. One report indicated that in TFE3‐positive RCCs the diagnosis of a high Fuhrman grade (III/IV) was made in 87.5% of cases and the 5‐year cancer‐specific survival rate was low (15.6%) [25]. In our study, six cases (75%) also showed higher Fuhrman grade (III/IV).…”

Section: Discussionmentioning

confidence: 99%

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The preliminary experiences of translocation renal cell carcinoma and literature review

Sung

Chiang

et al. 2014

The Kaohsiung J of Med Scie

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Xp11.2 translocation renal cell carcinoma (RCC) is rare and predominantly found in children and young adults. Because of the property of overexpressed transcription factor E3 (TFE3) fusion protein, immunohistochemical (IHC) staining with TFE3 antibody makes an excellent diagnostic tool. This study analyzed preliminary experiences of eight Xp11.2 translocation RCCs in our institution between 2007 and 2012. In four males and four females with a mean age of 28.4 years. Xp11.2 translocation RCCs were diagnosed. TFE3 IHC stain was positive in all tumor specimens. As the initial presentation, four patients suffered from abdominal pain, three cases had gross hematuria, and one case had hemoptysis caused by existing lung metastasis. The tumor was located in the right kidney (75%) with mean diameter of 5.85 ± 2.64 cm. Three cases (38%, 3/8) presented with lymph node metastasis at the time of diagnosis. In five cases (63%, 5/8), the initial diagnosis was Stage III and IV. Treatment included open surgery (one partial nephrectomy and five radical nephrectomies), cryoablation, immunotherapy, and target therapy. The mean follow-up time was 32 months. One patient died after 23.4 months of follow-up. The application of TFE3 IHC stain will improve the diagnostic accuracy for detecting XP11.2 translocation renal cell carcinoma. Surgery or cryoablation both had excellent prognosis in early stages. Although the disease is believed to be indolent, an increasingly aggressive clinical course should be kept in mind, especially for children and young adults.

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Section: Discussioncontrasting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

The preliminary experiences of translocation renal cell carcinoma and literature review

Sung

Chiang

et al. 2014

The Kaohsiung J of Med Scie

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“…In unclassified cases of RCC, adverse clinicopathological parameters are associated with positive expression of transcription factor E3 (TFE3) [3]. Studies have shown that the 5-year cancer-specific survival rate for TFE3-positive patients was 15.6% as compared to 87.5% for TFE3-negative patients [3].…”

Section: Discussionmentioning

confidence: 99%

“…Studies have shown that the 5-year cancer-specific survival rate for TFE3-positive patients was 15.6% as compared to 87.5% for TFE3-negative patients [3]. TFE3 positivity in RCC was significantly associated with shorter cancer specific survival ( P < 0.001).…”

Section: Discussionmentioning

confidence: 99%

Renal Cell Carcinoma Associated with Xp11.2 Translocation/TFE3 Gene Fusion: A Rare Case Report with Review of the Literature

Ahluwalia

Nair

Kumar

2013

Case Reports in Urology

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Introduction. The recently recognized renal cell carcinomas associated with Xp11.2 translocations are rare tumors predominantly reported in children. Chromosome Xp11.2 translocation results in gene fusion related to transcription factor E3 (TFE3) that plays an important role in proliferation and survival. Case Report. Herein, we present two cases of a TFE3 translocation-associated RCC in young female adults, one detected incidentally and the other one presenting with gross hematuria. Tumor is characterized by immunohistochemistry and a literature review with optimal treatment regimen is presented. Discussion. Xp11.2 translocation RCCs in adult patients are associated with advanced stages, large tumors, and extracapsular disease and usually have an aggressive clinical course. Conclusion. In TFE3 RCC, the genetic background may not only contribute to tumorigenesis, but also determine the response to chemotherapy and targeted therapy. Therefore it is necessary to diagnose this tumor entity accurately. Because of the small number of TFE3 gene fusion-related renal tumors described in the literature, the exact biologic behavior and impact of current treatment modalities remain to be uncertain.

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“…78-80 (Table 1) In RCC patients, higher TFE3 expression correlates independently with worse patient outcomes. 81,82 …”

Section: Mechanism Of Tfe-fusion Oncogenesis: Dysregulated Protein mentioning

confidence: 99%

Molecular genetics and cellular features of TFE3 and TFEB fusion kidney cancers

et al. 2014

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Despite nearly two decades since the discovery of gene fusions involving TFE3 or TFEB (“TFE”) in sporadic renal cell carcinoma (RCC), the molecular mechanisms underlying the renal-specific tumorigenesis remains largely unclear. The recent publication of the TCGA Network's clear cell kidney cancer paper provides further evidence for the importance of gene fusions by identifying 5 tumors harboring SFPQ-TFE3 fusions that otherwise lacked the common clear cell RCC associated mutation. Herein, we review key molecular features of TFE-fusion RCC, including candidate signaling pathways contributing to oncogenesis and a detailed overview of gene fusion isoforms based on an updated knowledge of TFE genetic organization. A total of 5 TFE3 gene fusions (PRCC-TFE3, ASPSCR1-TFE3, SFPQ-TFE3, NONO-TFE3, CLTC-TFE3) and 1 TFEB gene fusion (MALAT1-TFEB) have been identified in RCC tumors and characterized at the mRNA transcript level, with considerable heterogeneity in exon structure across different tumors, even for the same fusion partners. Common to all TFE3 and TFEB fusion isoforms is the retention of the wild-type protein C-terminus, including domains for DNA-binding, dimerization, and nuclear localization, but interestingly, not transcriptional activation. Despite this, the most widely accepted model explaining TFE-fusion oncogenesis remains the introduction of a constitutively active promoter leading to dysregulated TFE transcriptional activity. A multitude of molecular pathways well-implicated in carcinogenesis are regulated in part by TFE3 and/or TFEB protein, including activation of TGFβ and ETS transcription factors, E-cadherin expression, CD40L-dependent lymphocyte activation, mTORC1 signaling, insulin-dependent metabolism regulation, folliculin signaling, and Rb-dependent cell cycle arrest. Determining which pathways are most important will be critical to discovering the most promising therapeutic targets for this disease. Useful to this goal is a panel of cell lines derived from different TFE3-fusion RCC patient tumors, representing multiple fusion isoforms.

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Altered transcription factor E3 expression in unclassified adult renal cell carcinoma indicates adverse pathological features and poor outcome

Cited by 34 publications

References 19 publications

The preliminary experiences of translocation renal cell carcinoma and literature review

The preliminary experiences of translocation renal cell carcinoma and literature review

Renal Cell Carcinoma Associated with Xp11.2 Translocation/TFE3 Gene Fusion: A Rare Case Report with Review of the Literature

Molecular genetics and cellular features of TFE3 and TFEB fusion kidney cancers

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