The microphthalmia(MiT)subfamily of transcription factors includes TFE3,TFEB,TFEC,and MITF.In the 2016 World Health Organization classification,MiT family translocation renal cell carcinoma(tRCC)including Xp11 tRCC an...The microphthalmia(MiT)subfamily of transcription factors includes TFE3,TFEB,TFEC,and MITF.In the 2016 World Health Organization classification,MiT family translocation renal cell carcinoma(tRCC)including Xp11 tRCC and t(6;11)RCC,was newly defined as an RCC subtype.Xp11 and t(6;11)RCC are characterized by the rearrangement of the MiT transcription factors TFE3 and TFEB,respectively.Recent studies identified the fusion partner-dependent clinicopathological and immunohistochemical features in TFE3-rearranged RCC.Furthermore,RCC with TFEB amplification,melanotic MiT family translocation neoplasms,was identified may as a unique subtype of MiT family associated renal neoplasms,along with MITF associated RCC.In this review,we will collect available literature of these newly-described RCCs,analyze their clinicopathological and immunohistochemical features,and summarize their molecular and genetic evidences.We expect this review would be beneficial for the understanding of these rare subtypes of RCCs,and eventually promote clinical management strategies.展开更多
Background:In many cancer types,aryl hydrocarbon receptor nuclear translocator 2(ARNT2)has been found to be associated with tumor cell proliferation and prognosis.However,the role of ARNT2 in clear cell renal cell car...Background:In many cancer types,aryl hydrocarbon receptor nuclear translocator 2(ARNT2)has been found to be associated with tumor cell proliferation and prognosis.However,the role of ARNT2 in clear cell renal cell carcinoma(ccRCC)has not been completely elucidated.In this study,the potential role of ARNT2 in ccRCC development was characterized.Methods:A pan-cancer dataset(TCGA-TARGET-GTEx)was accessed from UCSC Xena Data Browser.ARNT2 expression in normal and tumor samples was compared.Univariate Cox regression was performed to evaluate the prognostic value of ARNT2.Single sample gene set enrichment analysis(ssGSEA)was used to estimate the enrichment of functional pathways and gene signatures.CIBERSORT and ESTIMATE methods evaluated the immune infiltration.The ARNT2 expression was determined in ccRCC tissue and cell lines using RT-qPCR and Western blot.Results:ARNT2 expression was significantly dysregulated in 23 out of 30 cancer types.Pan-cancer data revealed a strong correlation between ARNT2 expression and immune modulators,immune cell infiltration,and genomic alternations.In ccRCC patients,the low-ARNT2 expression group had higher immune infiltration,CD8 T cells,and programmed cell death ligand 1 expression,as well as higher enrichment score of immunotherapeutic predictors than those in the high-ARNT2 expression group.Low-ARNT2 expression group was more responsive to immunotherapy.Moreover,low ARNT2 expression was observed in ccRCC tissue and cell lines.Conclusions:Dysregulated ARNT2 expression is involved in cancer development and the modulation of the immune microenvironment.ARNT2 can be potentially used as a prognostic indicator and an immunotherapeutic indicator for ccRCC.展开更多
Gene fusions involving two of the MiT subfamily factors, such as TFE3, TFEB, TFC and MiTF, have been identified in renal cell carcinoma (RCC). Xp11.2 translocation RCC is a rare pediatric neoplasm that harbors gene fu...Gene fusions involving two of the MiT subfamily factors, such as TFE3, TFEB, TFC and MiTF, have been identified in renal cell carcinoma (RCC). Xp11.2 translocation RCC is a rare pediatric neoplasm that harbors gene fusions involving TFE3, which plays an important role in cell proliferation and survival. We herein present a case of RCC associated with Xp11.2 translocation/TFE3 gene fusion in a 14-year-old Japanese boy presenting gross hematuria and body weight loss. The tumor was characterized by histopathology, cytology and TFE3-immunohistochemistry/immunocytochemistry. Knowledge of distinctive morphological and immunostaining features of this tumor can help to accurately diagnose this rare subset of translocation associated RCC in routine pathological diagnostic procedures.展开更多
Our knowledge of renal cell carcinoma(RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and...Our knowledge of renal cell carcinoma(RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and defined, and our understanding of the biology and clinical correlates of these tumors is changing. Evolving concepts in Xp11 translocation carcinoma, mucinous tubular and spindle cell carcinoma, multilocular cystic clear cell RCC, and carcinoma associated with neuroblastoma are addressed within this review. Tubulocystic carcinoma, thyroid-like follicular carcinoma of kidney, acquired cystic disease-associated RCC, and clear cell papillary RCC are also described. Finally, candidate entities, including RCC with t(6;11) translocation, hybrid oncocytoma/chromophobe RCC, hereditary leiomyomatosis and RCC syndrome, and renal angiomyoadenomatous tumor are reviewed. Knowledge of these new entities is important for diagnosis, treatment and subsequent prognosis. This review provides a targeted summary of new developments in RCC.展开更多
Microphthalmia-associated transcription factor family(transcription factor E3 or transcription factor EB)translocation renal cell carcinomas(RCCs)are rare neoplasms.These renal neoplasms can be either asymptomatic and...Microphthalmia-associated transcription factor family(transcription factor E3 or transcription factor EB)translocation renal cell carcinomas(RCCs)are rare neoplasms.These renal neoplasms can be either asymptomatic and incidentally discovered on imaging or symptomatic,with the most common presenting symptoms being hematuria,pain,and abdominal mass,or paraneoplastic event.In conventional RCCs,hypertension is considered a risk factor and a possible paraneoplastic event,whereas,in translocation RCCs,prior exposure to cytotoxic chemotherapy is the only known risk factor,and hypertension as an isolated associated paraneoplastic event has never been reported.Interestingly,hypertension as the only presenting symptom in RCC is extremely rare.We report a case of transcription factor E3 positive RCC in a young adult presenting only with hypertension that normalized after radical nephrectomy.To the best of our knowledge,this is the first reported case of hypertension secondary to microphthalmia-associated transcription translocation RCC.展开更多
文摘The microphthalmia(MiT)subfamily of transcription factors includes TFE3,TFEB,TFEC,and MITF.In the 2016 World Health Organization classification,MiT family translocation renal cell carcinoma(tRCC)including Xp11 tRCC and t(6;11)RCC,was newly defined as an RCC subtype.Xp11 and t(6;11)RCC are characterized by the rearrangement of the MiT transcription factors TFE3 and TFEB,respectively.Recent studies identified the fusion partner-dependent clinicopathological and immunohistochemical features in TFE3-rearranged RCC.Furthermore,RCC with TFEB amplification,melanotic MiT family translocation neoplasms,was identified may as a unique subtype of MiT family associated renal neoplasms,along with MITF associated RCC.In this review,we will collect available literature of these newly-described RCCs,analyze their clinicopathological and immunohistochemical features,and summarize their molecular and genetic evidences.We expect this review would be beneficial for the understanding of these rare subtypes of RCCs,and eventually promote clinical management strategies.
基金funded by the Shenzhen Longhua District Medical and Health Institutions Research Fund(Project No.2022102).
文摘Background:In many cancer types,aryl hydrocarbon receptor nuclear translocator 2(ARNT2)has been found to be associated with tumor cell proliferation and prognosis.However,the role of ARNT2 in clear cell renal cell carcinoma(ccRCC)has not been completely elucidated.In this study,the potential role of ARNT2 in ccRCC development was characterized.Methods:A pan-cancer dataset(TCGA-TARGET-GTEx)was accessed from UCSC Xena Data Browser.ARNT2 expression in normal and tumor samples was compared.Univariate Cox regression was performed to evaluate the prognostic value of ARNT2.Single sample gene set enrichment analysis(ssGSEA)was used to estimate the enrichment of functional pathways and gene signatures.CIBERSORT and ESTIMATE methods evaluated the immune infiltration.The ARNT2 expression was determined in ccRCC tissue and cell lines using RT-qPCR and Western blot.Results:ARNT2 expression was significantly dysregulated in 23 out of 30 cancer types.Pan-cancer data revealed a strong correlation between ARNT2 expression and immune modulators,immune cell infiltration,and genomic alternations.In ccRCC patients,the low-ARNT2 expression group had higher immune infiltration,CD8 T cells,and programmed cell death ligand 1 expression,as well as higher enrichment score of immunotherapeutic predictors than those in the high-ARNT2 expression group.Low-ARNT2 expression group was more responsive to immunotherapy.Moreover,low ARNT2 expression was observed in ccRCC tissue and cell lines.Conclusions:Dysregulated ARNT2 expression is involved in cancer development and the modulation of the immune microenvironment.ARNT2 can be potentially used as a prognostic indicator and an immunotherapeutic indicator for ccRCC.
文摘Gene fusions involving two of the MiT subfamily factors, such as TFE3, TFEB, TFC and MiTF, have been identified in renal cell carcinoma (RCC). Xp11.2 translocation RCC is a rare pediatric neoplasm that harbors gene fusions involving TFE3, which plays an important role in cell proliferation and survival. We herein present a case of RCC associated with Xp11.2 translocation/TFE3 gene fusion in a 14-year-old Japanese boy presenting gross hematuria and body weight loss. The tumor was characterized by histopathology, cytology and TFE3-immunohistochemistry/immunocytochemistry. Knowledge of distinctive morphological and immunostaining features of this tumor can help to accurately diagnose this rare subset of translocation associated RCC in routine pathological diagnostic procedures.
文摘Our knowledge of renal cell carcinoma(RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and defined, and our understanding of the biology and clinical correlates of these tumors is changing. Evolving concepts in Xp11 translocation carcinoma, mucinous tubular and spindle cell carcinoma, multilocular cystic clear cell RCC, and carcinoma associated with neuroblastoma are addressed within this review. Tubulocystic carcinoma, thyroid-like follicular carcinoma of kidney, acquired cystic disease-associated RCC, and clear cell papillary RCC are also described. Finally, candidate entities, including RCC with t(6;11) translocation, hybrid oncocytoma/chromophobe RCC, hereditary leiomyomatosis and RCC syndrome, and renal angiomyoadenomatous tumor are reviewed. Knowledge of these new entities is important for diagnosis, treatment and subsequent prognosis. This review provides a targeted summary of new developments in RCC.
文摘Microphthalmia-associated transcription factor family(transcription factor E3 or transcription factor EB)translocation renal cell carcinomas(RCCs)are rare neoplasms.These renal neoplasms can be either asymptomatic and incidentally discovered on imaging or symptomatic,with the most common presenting symptoms being hematuria,pain,and abdominal mass,or paraneoplastic event.In conventional RCCs,hypertension is considered a risk factor and a possible paraneoplastic event,whereas,in translocation RCCs,prior exposure to cytotoxic chemotherapy is the only known risk factor,and hypertension as an isolated associated paraneoplastic event has never been reported.Interestingly,hypertension as the only presenting symptom in RCC is extremely rare.We report a case of transcription factor E3 positive RCC in a young adult presenting only with hypertension that normalized after radical nephrectomy.To the best of our knowledge,this is the first reported case of hypertension secondary to microphthalmia-associated transcription translocation RCC.
