<i><scp>TFE</scp>3</i> translocation and protein expression in renal cell carcinoma are correlated with poor prognosis

Lee, Hyun Jung; Shin, Dong Hoon; Kim, So Young; Hwang, Chungsu; Lee, Jun Young; Park, Won Young; Choi, Kyung Un; Kim, Jee Yeon; Lee, Chang-Hun; Sol, Mee Young; Rha, Seo Hee; Park, Sung Woo

doi:10.1111/his.13700

Cited by 28 publications

(36 citation statements)

References 21 publications

(37 reference statements)

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“…This is the first comparative analysis, to our knowledge, of PD‐L1 expression in RCC tumours of different types, showing that TRCC exhibited the highest PD‐L1 positivity rate. Our previous study revealed that TFE3 expression in renal cell carcinoma is associated with a poor prognosis . TFE3 translocation is a possible source of immunogenic neoantigen and could stimulate T cell responses.…”

Section: Discussionsupporting

confidence: 90%

PD‐L1 expression and infiltration by CD4⁺ and FoxP3⁺ T cells are increased in Xp11 translocation renal cell carcinoma and indicate poor prognosis

et al. 2020

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Aims: Interaction between programmed death-1 ligand (PD-L1) and its receptor programmed death 1 (PD-1) on T cells inactivates antitumour immune responses. PD-L1 expression has been associated with poor prognosis in renal cell carcinoma (RCC) and predicts adverse outcome. This study was designed to evaluate the impact of PD-L1 expression and the immune microenvironment on the clinical outcome in Xp11 translocation renal cell carcinoma (TRCC) and, therefore, their potential relevance as prognostic biomarkers. Methods and results: The present retrospective analysis investigated expression of PD-L1 and immune cells CD8, CD4, CD3, forkhead box protein 3 (FoxP3) and PD-1 in TRCC compared to other types of RCC. FFPE specimens were collected between 2011 and 2017 from 311 patients who underwent nephrectomy at our institution for RCC. Specimens were immunostained for PD-L1, CD8, CD4, CD3, FoxP3 and PD-1, and an outcome analysis was conducted. PD-L1 expression rate was highest in TRCC (68%, 16 of 25), followed by mucinous tubular and spindle cell RCC and collecting duct carcinoma (33%, one of three), papillary RCC (27%, seven of 26), clear cell RCC (16%, 29 of 233), chromophobe RCC (11%, two of 18) and multilocular cystic RCC (0%, none of three). In TRCC, PD-L1 expression was associated with poor recurrence-free survival (RFS) (P = 0.041). The CD4 high and FoxP3 high groups showed a significantly shorter RFS (P = 0.05 and P = 0.031, respectively) compared to CD4 low and FOXP low groups. Conclusion: PD-L1 expression was higher in TRCC than in other types of RCC. High PD-L1 tumour cell expression and tumour infiltration by CD4 + and FoxP3 + immune cells were associated with poor RFS in TRCC.

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Section: Discussionsupporting

confidence: 90%

PD‐L1 expression and infiltration by CD4⁺ and FoxP3⁺ T cells are increased in Xp11 translocation renal cell carcinoma and indicate poor prognosis

et al. 2020

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“…Conversely, two cases with weak TFE3 expression (1+) had an Xp11 gene fusion. These findings are in line with prior reports of the relatively low specificity and predictive value of TFE3 IHC . TFE3 reactivity could be present in up to 9% of all IHC stained RCC cases detecting not only chimeric TFE3 fusion protein, but also cases with underlying TFE3 amplification and other mechanisms of transcriptional TFE3 activation, and often associated with more aggressive behavior .…”

Section: Discussionsupporting

confidence: 91%

“…Of patients with renal tRCCs, one third are children, one sixth are younger than 50, and 0.6% to 4% are older adults, although adult cases outnumber pediatric cases due the much greater incidence of renal cell carcinoma (RCC) in adults . In addition to affecting younger patients, tRCCs often present as high stage advanced disease and have poor outcomes that are likely similar to that of clear cell RCCs . Accurate diagnosis of tRCC is required for prognosis and guiding clinical management since these tumors are poorly responsive to targeted therapies developed for conventional RCC, but may benefit from novel treatment strategies such as dual PIK3/mTOR inhibition, siRNA‐mediated TFE3 silencing, and MET inhibitors .…”

Section: Introductionmentioning

confidence: 99%

Gene fusion analysis in renal cell carcinoma by FusionPlex RNA‐sequencing and correlations of molecular findings with clinicopathological features

Tretiakova

Wang

et al. 2019

Genes Chromosomes & Cancer

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Translocation renal cell carcinoma (tRCC) affects younger patients and often presents as advanced disease. Accurate diagnosis is required to guide clinical management.Here we evaluate the RNA-sequencing FusionPlex platform with a 115-gene panel including TFE3 and TFEB for tRCC diagnosis and correlate molecular findings with clinicopathological features. We reviewed 996 consecutive RCC cases from our institution over the preceding 7 years and retrieved 17 cases with histological and immunohistochemical features highly suggestive of either TFE3 (n = 16) or TFEB (n = 1).Moderate to strong labeling for TFE3 was present in 15 cases; two cases with weak TFE3 expression were melan-A or cathepsin-K positive. RNA-sequencing detected gene rearrangements in eight cases: PRCC-TFE3 (3), ASPSCR1-TFE3 (2), LUC7L3-TFE3(1), SFPQ-TFE3 (1), and a novel SETD1B-TFE3 (1). FISH assays of 11 tumors verified six positive cases concordant with FusionPlex analysis results. Two other cases were confirmed by RT-PCR. FusionPlex was superior to FISH by providing precise breakpoints for tRCC-related genes in a single assay and allowing identification of both known and novel fusion partners, thereby facilitating clinicopathological correlations as fusion partners can influence tumor appearance, immunophenotype, and behavior. Cases with partner genes PRCC and novel partner SETD1B were associated with prominent papillary architecture while cases with partner genes ASPSCR1 and LUC7L3 were associated with a predominantly nested/alveolar pattern. The case with SFPQ-TFE3 fusion was characterized by biphasic morphology mimicking TFEB-like translocation RCC. We recommend FusionPlex analysis of RCC in patients under age 50 or when the histologic appearance suggests tRCC. K E Y W O R D S anchored multiplex PCR (AMP), FusionPlex, MiT family, RNA-seq, translocation renal cell carcinoma

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“…1 Approximately one-third patients have metastasis when diagnosed as RCC, 2 so it is urgent to find a new molecular biomarker for RCC diagnosis at the early stage. As reported, genetic biomarkers for RCC have been widely investigated including molecules [3][4][5] and microRNAs (miRNAs). 6,7 miRNAs is a class of endogenous small non-coding RNAs, the length of which is approximately 19-22 nucleotides.…”

Section: Introductionmentioning

confidence: 99%

<p>miR-106b promotes proliferation and invasion by targeting Capicua through MAPK signaling in renal carcinoma cancer</p>

Miao¹,

Shu²,

Zhuang³

et al. 2019

OTT

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Background: miR-106b has been reported to play a vital role in pathogenesis of some types of cancer, whilst the role of miR-106b in renal carcinoma cancer (RCC) remains unknown. Purpose: The objective of this study was to identify the mechanism of miR-106b regulating the progression of renal carcinoma. Method: The expression of miR-106b was analyzed in RCC cell lines, RCC and adjacent normal renal tissues through qRT-PCR assays. Target mRNA of miR-106b was predicted with databases and verified by luciferase reporter assays. And the effects of miR-106b or targeted mRNA on cell proliferation, invasion, the process of epithelial-mesenchymal transitions (EMTs) were assessed in vitrothrough CCK-8, transwell cell invasion assays, qRT-PCR and Western blotting assays respectively. In addition, the effects of miR-106b on the growth of xenografts mice were analyzedin vivo. Results: The results demonstrated that miR-106b was significantly increased both in RCC tissues and cell lines. Luciferase reporter assays revealed that miR-106b inhibited Capicua expression by targeting its 3ʹ-UTR sequence. And miR-106b promoted cell proliferation, invasion, EMT progression in RCC cellin vitro, as well as promoted the tumor growth of 786-O cells derived xenografts mice. Additionally, loss of Capicua promoted the activation of MAPK signaling pathway. Conclusion: The study suggested that miR-106b regulated RCC progression through MAPK signaling pathway partly by targeting Capicua, which might provide valuable evidence for therapeutic target development of RCC.

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TFE3 translocation and protein expression in renal cell carcinoma are correlated with poor prognosis

Abstract: Increased TFE3 expression in RCC was associated with poor PFS regardless of the gene translocation status. Moreover, morphological analysis should help to select candidates who would benefit from TFE3 staining and FISH analysis.

Cited by 28 publications

References 21 publications

PD‐L1 expression and infiltration by CD4⁺ and FoxP3⁺ T cells are increased in Xp11 translocation renal cell carcinoma and indicate poor prognosis

PD‐L1 expression and infiltration by CD4⁺ and FoxP3⁺ T cells are increased in Xp11 translocation renal cell carcinoma and indicate poor prognosis

Gene fusion analysis in renal cell carcinoma by FusionPlex RNA‐sequencing and correlations of molecular findings with clinicopathological features

<p>miR-106b promotes proliferation and invasion by targeting Capicua through MAPK signaling in renal carcinoma cancer</p>

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TFE3 translocation and protein expression in renal cell carcinoma are correlated with poor prognosis

Abstract: Increased TFE3 expression in RCC was associated with poor PFS regardless of the gene translocation status. Moreover, morphological analysis should help to select candidates who would benefit from TFE3 staining and FISH analysis.

Cited by 28 publications

References 21 publications

PD‐L1 expression and infiltration by CD4+ and FoxP3+ T cells are increased in Xp11 translocation renal cell carcinoma and indicate poor prognosis

PD‐L1 expression and infiltration by CD4+ and FoxP3+ T cells are increased in Xp11 translocation renal cell carcinoma and indicate poor prognosis

Gene fusion analysis in renal cell carcinoma by FusionPlex RNA‐sequencing and correlations of molecular findings with clinicopathological features

<p>miR-106b promotes proliferation and invasion by targeting Capicua through MAPK signaling in renal carcinoma cancer</p>

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PD‐L1 expression and infiltration by CD4⁺ and FoxP3⁺ T cells are increased in Xp11 translocation renal cell carcinoma and indicate poor prognosis

PD‐L1 expression and infiltration by CD4⁺ and FoxP3⁺ T cells are increased in Xp11 translocation renal cell carcinoma and indicate poor prognosis