Clear-cell sarcoma is a rare, malignant soft tissue tumor that displays melanocytic differentiation with a distinct molecular profile. It is rarely localized in the gastrointestinal tract. Herein we reported a case of...Clear-cell sarcoma is a rare, malignant soft tissue tumor that displays melanocytic differentiation with a distinct molecular profile. It is rarely localized in the gastrointestinal tract. Herein we reported a case of multiple synchronous clear-cell sarcomas of the gastrointestinal tract with parotid gland metastasis. A 51-year-old male patient presented with a growing painless mass under the right ear. A preoperative positron emission tomography/computed tomography showed multiple intestinal masses and a mass in the right parotid with increased glucose uptake, and he underwent operative treatment with resection of three tumors in the jejunum and ileum and then received a right parotidectomy. Postoperative pathological examination showed that cells in the intestinal tumor were consistent with clear-cell sarcoma of the gastrointestinal tract, and the malignant cells in the parotid gland were similar to the intestinal tumor. Immunohistochemical studies revealed positive expression of HMB-45, Melan-A, and S-100. EWSR1 gene fusion transcripts were undetectable by fluorescence in situ hybridization.展开更多
We report here the case of a young patient with metastatic clear-cell sarcoma of the kidney resistant to standard chemotherapy, and with complete response under sorafenib treatment. The remarkable response of her tumo...We report here the case of a young patient with metastatic clear-cell sarcoma of the kidney resistant to standard chemotherapy, and with complete response under sorafenib treatment. The remarkable response of her tumor to sorafenib led us to study sorafenib molecular targets in the metastatic tissue. Background: Biomarkers predicting response to anti-angiogenic tyrosine kinase inhibitors remain to be identified. Methods and Findings: In this paper, we studied the molecular targets of sorafenib in the lung metastasis of a kidney clear-cell sarcoma. In a patient with complete response under sorafenib treatment, we showed high VEGFR2 expression by tumor endothelial cells from the lung metastasis. Conclusion: The original mechanistic results that we obtained using immunostainings and quantitative RT-PCR on laser-microdissected tumor endothelial cells have a direct application in daily clinical practice: metastatic tumors with a large angiogenic component should be tested for VEGFRs expression to consider anti-angiogenic tyrosine kinase inhibitor treatments.展开更多
Objective To identify new genes that correlate with prognosis of clear-cell renal cell carcinoma(ccRCC)via bioinformatics analysis.Methods The gene expression profiles of 62 ccRCC and 54 normal kidney tissues were ava...Objective To identify new genes that correlate with prognosis of clear-cell renal cell carcinoma(ccRCC)via bioinformatics analysis.Methods The gene expression profiles of 62 ccRCC and 54 normal kidney tissues were available from the Gene Expression Omnibus database:GSE12606,GSE36895 and GSE66272.The differentially expressed genes were screened with GEO2R and J Venn online tools.Functional annotation including Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)was applied to identify the possible function of the hub genes involved in prognosis of ccRCC.In protein protein interaction network(PPI network),the STRING online tool was used to visualize the network of the differentially expressed genes,and the core gene was selected by MCODE App in Cytoscape software.Finally,GEPIA Survival Plot was performed to assess genes associated with worse survival.Results We totally found 648 diflerentially expressed genes,including 222 up-regulated genes and 426 down-regulated genes.PPI network showed that in 28 up-regulated genes 7(CCNE2,CDK1,CDC6,CCNB2,BUB1,TTK and PTTG1)enriched in cell cycle and 4 genes(CCNE2,CDK1,CCNB2 and RRM2)enriched in p53 signaling pathway.GEPIA Survival Plot assay revealed that ccRCC patients carrying CDK1,CCNB2,RRM2t BUB1,and PTTG1 had a worse survival.GEPIA Box Plot showed that BUB1,CCNB2,PTTG1,and RRM2 were over expressed in the ccRCC tissues in contrast to the normal tissues(P<O.OS).Conclusion ccRCC patients with the four up-regulated differentially expressed genes including BUB1,CCNB2,PTTG1,and RRM2 might manifest a poor prognosis.展开更多
A 36-year-old woman was admitted to our department for close examination of a liver tumor that was found during a medical checkup. Abdominal US, CT and MRI showed a tumor in segment 7 (S7) of the liver. Although imagi...A 36-year-old woman was admitted to our department for close examination of a liver tumor that was found during a medical checkup. Abdominal US, CT and MRI showed a tumor in segment 7 (S7) of the liver. Although imaging suggested hepatocellular carcinoma, laboratory tests showed no abnormality in liver function, hepatitis virus markers were negative, and tumor markers including protein induced by vitamin K absence or antagonist Ⅱ (PIVKA-Ⅱ), α-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) were all within normal ranges. Upon aspiration biopsy of the liver, the histopathological diagnosis was moderately differentiated hepatocellular carcinoma. Therefore, right hepatectomy was performed. Although a part of the tumor was necrotic, about 60% of the viable part showed a clear-cell variant. Consequently, it was diagnosed as clear-cell hepatocellular carcinoma. It was noted that the background liver tissue was normal. This case is worthy of reporting because development of clear-cell hepatocellular carcinoma in the normal liver of a middle-aged woman is rarely seen.展开更多
We present an uncommon case (female patient aged 59 years) of the clear-cell variant of calcifying epithelial odontogenic tumor (CEOT) (also known as Pindborg tumor) in the mandible. The clinical characteristics...We present an uncommon case (female patient aged 59 years) of the clear-cell variant of calcifying epithelial odontogenic tumor (CEOT) (also known as Pindborg tumor) in the mandible. The clinical characteristics and probable origins of the clear tumor cells of previously reported cases of clear-cell variant of intraosseous CEOT are also summarized and discussed.展开更多
Background:Lymphatic metastasis is one of the most common metastatic routes and indicates a poor prognosis in clear-cell renal cell carcinoma(ccRCC).N-acetyltransferase 10(NAT10)is known to catalyze N4-acetylcytidine(...Background:Lymphatic metastasis is one of the most common metastatic routes and indicates a poor prognosis in clear-cell renal cell carcinoma(ccRCC).N-acetyltransferase 10(NAT10)is known to catalyze N4-acetylcytidine(ac4C)modification of mRNA and participate in many cellular processes.However,its role in the lymphangiogenic process of ccRCC has not been reported.This study aimed to elucidate the role of NAT10 in ccRCC lymphangiogenesis,providing valuable insights into potential therapeutic targets for intervention.Methods:ac4C modification and NAT10 expression levels in ccRCC were assessed using public databases and clinical samples.Functional investigations involved manipulating NAT10 expression in cellular and mouse models to study its role in ccRCC.Mechanistic insights were gained through a combination of RNA sequencing,mass spectrometry,co-immunoprecipitation,RNA immuno-precipitation,immunofluorescence,and site-specific mutation analyses.Results:We found that ac4C modification and NAT10 expression levels increased in ccRCC.NAT10 promoted tumor progression and lymphangiogene-sis of ccRCC by enhancing the nuclear import of Yes1-associated transcriptional regulator(YAP1).Subsequently,we identified ankyrin repeat and zinc fin-ger peptidyl tRNA hydrolase 1(ANKZF1)as the functional target of NAT10,and its upregulation in ccRCC was caused by NAT10-mediated ac4C modifi-cation.Mechanistic analyses demonstrated that ANKZF1 interacted with tyro-sine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon(YWHAE)to competitively inhibit cytoplasmic retention of YAP1,leading to transcriptional activation of pro-lymphangiogenic factors.Conclusions:These results suggested a pro-cancer role of NAT10-mediated acetylation in ccRCC and identified the NAT10/ANKZF1/YAP1 axis as an under-reported pathway involving tumor progression and lymphangiogenesis in ccRCC.展开更多
Due to the complicated histopathological characteristics of clear-cell renal-cell carcinoma(ccRcC),non-invasive prognosis before operative treatment is crucial in selecting the appropriate treatment.A total of 126345 ...Due to the complicated histopathological characteristics of clear-cell renal-cell carcinoma(ccRcC),non-invasive prognosis before operative treatment is crucial in selecting the appropriate treatment.A total of 126345 computerized tomography(cT)images from four independent patient cohorts were included for analysis in this study.We propose a V Bottieneck multi-resolution and focus-organ network(VB-MrFo-Net)using a cascade framework for deep learning analysis.The VB-MrFo-Net achieved better performance than VB-Net in tumor segmentation,with a Dice score of 0.87.The nuclear-grade prediction model performed best in the logistic regression classifier,with area under curve values from 0.782 to 0.746.Survival analysis revealed that our prediction model could significantly distinguish patients with high survival risk,with a hazard ratio(HR)of 2.49[95%confidence interval(CI):1.13-5.45,P=0.023]in the General cohort.Excellent performance had also been verified in the Cancer Genome Atlas cohort,the Clinical Proteomic Tumor Analysis Consortium cohort,and the Kidney Tumor Segmentation Challenge cohort,with HRs of 2.77(95%CI:1.58-4.84,P=0.0019),3.83(95%CI:1.22-11.96,P=0.029),and 2.80(95%CI:1.05-7.47,P=0.025),respectively.In conclusion,we propose a novel VB-MrFo-Net for the renal tumor segmentation and automatic diagnosis of ccRcc.The risk stratification model could accurately distinguish patients with high tumor grade and high survival risk based on non-invasive CT images before surgical treatments,which couid provide practical advicefordecidingtreatmentoptions.展开更多
Renal-cell carcinoma(RCC)remains a leading cause of cancer-related mortality worldwide.Though newer therapeutic combinations of immune checkpoint inhibitors and targeted therapies have greatly improved outcomes,resist...Renal-cell carcinoma(RCC)remains a leading cause of cancer-related mortality worldwide.Though newer therapeutic combinations of immune checkpoint inhibitors and targeted therapies have greatly improved outcomes,resistance to these therapies is becoming a challenge for long-term control.Mechanisms of resistance have been explored in a variety of solid tumors,including RCC.Based upon our review of the current literature on the mechanisms of resistance to immunotherapies for the management of metastatic clear-cell renal cell carcinomas(mccRCC),the ensuing conclusions have been made:The management of mccRCC has progressed substantially with the advent of checkpoint inhibitors and targeted oral therapies,alone and/or in combination.Nevertheless,innate or developed resistance to these therapies remains an ongoing challenge,particularly to immune checkpoint inhibitors(ICIs).Several of the known mechanisms of resistance have been well defined,but recent progression in cellular therapies helps to expand the armamentarium of potential combination options that may overcome these modes of resistance and improve long-term disease control and survival for an otherwise dismal disease.In the ensuing review and update of the literature on the mechanisms of resistance to immunotherapies in mccRCC,we have revisited the known resistance mechanisms of immunotherapies in metastatic clear-cell RCC and explored ongoing and future strategies to overcome them.展开更多
Background:Vascular endothelial growth factor-targeted agents are standard treatments in advanced clear-cell renal cell carcinoma (ccRCC),but biomarkers of activity are lacking.The aim of this study was to investig...Background:Vascular endothelial growth factor-targeted agents are standard treatments in advanced clear-cell renal cell carcinoma (ccRCC),but biomarkers of activity are lacking.The aim of this study was to investigate the association of Von Hippel-Lindau (VHL) gene status,vascular endothelial growth factor receptor (VEGFR) or stem cell factor receptor (KIT) expression,and their relationships with characteristics and clinical outcome of advanced ccRCC.Methods:A total of 59 patients who received targeted treatment with sunitinib or pazopanib were evaluated for determination at Cancer Hospital and Institute,Chinese Academy of Medical Sciences between January 2010 and November 2012.Paraffin-embedded tumor samples were collected and status of the VHL gene and expression of VEGFR and KIT were determined by VHL sequence analysis and immunohistochemistry.Clinical-pathological features were collected and efficacy such as response rate and Median progression-free survival (PFS) and ovcrall survival (OS) were calculated and then compared based on expression status.The Chi-square test,the KaplanMeier method,and the Lon-rank test were used for statistical analyses.Results:Of 59 patients,objective responses were observed in 28 patients (47.5%).The median PFS was 13.8 months and median OS was 39.9 months.There was an improved PFS in patients with the following clinical features:Male gender,number of metastatic sites 2 or less,VEGFR-2 positive or KIT positive.Eleven patients (18.6%) had evidence of VHL mutation,with an objective response rate of 45.5%,which showed no difference with patients with no VHL mutation (47.9%).VHL mutation status did not correlate with either overall response rate (P =0.938) or PFS (P =0.277).The PFS was 17.6 months and 22.2 months in VEGFR-2 positive patients and KIT positive patients,respectively,which was significantly longer than that of VEGFR-2 or KIT negative patients (P =0.026 and P =0.043).Conclusion:VHL mutation status could not predict the efficacy of sunitinib or pazopanib.Further investigation of VHL/VEGFR pathway components is needed.展开更多
基金Supported by Basic Scientific Research Business of Chinese Academy of Medical Sciences,No.2016ZX310020
文摘Clear-cell sarcoma is a rare, malignant soft tissue tumor that displays melanocytic differentiation with a distinct molecular profile. It is rarely localized in the gastrointestinal tract. Herein we reported a case of multiple synchronous clear-cell sarcomas of the gastrointestinal tract with parotid gland metastasis. A 51-year-old male patient presented with a growing painless mass under the right ear. A preoperative positron emission tomography/computed tomography showed multiple intestinal masses and a mass in the right parotid with increased glucose uptake, and he underwent operative treatment with resection of three tumors in the jejunum and ileum and then received a right parotidectomy. Postoperative pathological examination showed that cells in the intestinal tumor were consistent with clear-cell sarcoma of the gastrointestinal tract, and the malignant cells in the parotid gland were similar to the intestinal tumor. Immunohistochemical studies revealed positive expression of HMB-45, Melan-A, and S-100. EWSR1 gene fusion transcripts were undetectable by fluorescence in situ hybridization.
文摘We report here the case of a young patient with metastatic clear-cell sarcoma of the kidney resistant to standard chemotherapy, and with complete response under sorafenib treatment. The remarkable response of her tumor to sorafenib led us to study sorafenib molecular targets in the metastatic tissue. Background: Biomarkers predicting response to anti-angiogenic tyrosine kinase inhibitors remain to be identified. Methods and Findings: In this paper, we studied the molecular targets of sorafenib in the lung metastasis of a kidney clear-cell sarcoma. In a patient with complete response under sorafenib treatment, we showed high VEGFR2 expression by tumor endothelial cells from the lung metastasis. Conclusion: The original mechanistic results that we obtained using immunostainings and quantitative RT-PCR on laser-microdissected tumor endothelial cells have a direct application in daily clinical practice: metastatic tumors with a large angiogenic component should be tested for VEGFRs expression to consider anti-angiogenic tyrosine kinase inhibitor treatments.
基金the National Technical system of Chinese Medicinal Materials Industry(No.CARS-21)the Key Natural Science Projects of West Anhui University in China(No.WXZR201932)+4 种基金the Training Program of Innovate and Entrepreneurship of National College students in China(No.201810376058,201810376061)Anhui Provincial Natural Science Foundation in China(No.2017A030311022)Anhui Provincial University Natural Science Project in China(No.KJ2018A0413,KJ2017a407)Anhui Provincial Quality of Undergraduate project in China(No.2018zygc075,2018jyxm1153,2018jyxm1155)the Teaching and Research Projects of West Anhui University in China(No.wxxy2018026).
文摘Objective To identify new genes that correlate with prognosis of clear-cell renal cell carcinoma(ccRCC)via bioinformatics analysis.Methods The gene expression profiles of 62 ccRCC and 54 normal kidney tissues were available from the Gene Expression Omnibus database:GSE12606,GSE36895 and GSE66272.The differentially expressed genes were screened with GEO2R and J Venn online tools.Functional annotation including Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)was applied to identify the possible function of the hub genes involved in prognosis of ccRCC.In protein protein interaction network(PPI network),the STRING online tool was used to visualize the network of the differentially expressed genes,and the core gene was selected by MCODE App in Cytoscape software.Finally,GEPIA Survival Plot was performed to assess genes associated with worse survival.Results We totally found 648 diflerentially expressed genes,including 222 up-regulated genes and 426 down-regulated genes.PPI network showed that in 28 up-regulated genes 7(CCNE2,CDK1,CDC6,CCNB2,BUB1,TTK and PTTG1)enriched in cell cycle and 4 genes(CCNE2,CDK1,CCNB2 and RRM2)enriched in p53 signaling pathway.GEPIA Survival Plot assay revealed that ccRCC patients carrying CDK1,CCNB2,RRM2t BUB1,and PTTG1 had a worse survival.GEPIA Box Plot showed that BUB1,CCNB2,PTTG1,and RRM2 were over expressed in the ccRCC tissues in contrast to the normal tissues(P<O.OS).Conclusion ccRCC patients with the four up-regulated differentially expressed genes including BUB1,CCNB2,PTTG1,and RRM2 might manifest a poor prognosis.
文摘A 36-year-old woman was admitted to our department for close examination of a liver tumor that was found during a medical checkup. Abdominal US, CT and MRI showed a tumor in segment 7 (S7) of the liver. Although imaging suggested hepatocellular carcinoma, laboratory tests showed no abnormality in liver function, hepatitis virus markers were negative, and tumor markers including protein induced by vitamin K absence or antagonist Ⅱ (PIVKA-Ⅱ), α-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) were all within normal ranges. Upon aspiration biopsy of the liver, the histopathological diagnosis was moderately differentiated hepatocellular carcinoma. Therefore, right hepatectomy was performed. Although a part of the tumor was necrotic, about 60% of the viable part showed a clear-cell variant. Consequently, it was diagnosed as clear-cell hepatocellular carcinoma. It was noted that the background liver tissue was normal. This case is worthy of reporting because development of clear-cell hepatocellular carcinoma in the normal liver of a middle-aged woman is rarely seen.
文摘We present an uncommon case (female patient aged 59 years) of the clear-cell variant of calcifying epithelial odontogenic tumor (CEOT) (also known as Pindborg tumor) in the mandible. The clinical characteristics and probable origins of the clear tumor cells of previously reported cases of clear-cell variant of intraosseous CEOT are also summarized and discussed.
基金This study was supported by the National Natural Sci-ence Foundation of China(81874090,81972630,82202911,82300786).
文摘Background:Lymphatic metastasis is one of the most common metastatic routes and indicates a poor prognosis in clear-cell renal cell carcinoma(ccRCC).N-acetyltransferase 10(NAT10)is known to catalyze N4-acetylcytidine(ac4C)modification of mRNA and participate in many cellular processes.However,its role in the lymphangiogenic process of ccRCC has not been reported.This study aimed to elucidate the role of NAT10 in ccRCC lymphangiogenesis,providing valuable insights into potential therapeutic targets for intervention.Methods:ac4C modification and NAT10 expression levels in ccRCC were assessed using public databases and clinical samples.Functional investigations involved manipulating NAT10 expression in cellular and mouse models to study its role in ccRCC.Mechanistic insights were gained through a combination of RNA sequencing,mass spectrometry,co-immunoprecipitation,RNA immuno-precipitation,immunofluorescence,and site-specific mutation analyses.Results:We found that ac4C modification and NAT10 expression levels increased in ccRCC.NAT10 promoted tumor progression and lymphangiogene-sis of ccRCC by enhancing the nuclear import of Yes1-associated transcriptional regulator(YAP1).Subsequently,we identified ankyrin repeat and zinc fin-ger peptidyl tRNA hydrolase 1(ANKZF1)as the functional target of NAT10,and its upregulation in ccRCC was caused by NAT10-mediated ac4C modifi-cation.Mechanistic analyses demonstrated that ANKZF1 interacted with tyro-sine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon(YWHAE)to competitively inhibit cytoplasmic retention of YAP1,leading to transcriptional activation of pro-lymphangiogenic factors.Conclusions:These results suggested a pro-cancer role of NAT10-mediated acetylation in ccRCC and identified the NAT10/ANKZF1/YAP1 axis as an under-reported pathway involving tumor progression and lymphangiogenesis in ccRCC.
基金supported by the National Natural Science Foundation of China(Grants No.81972393 and 82002665).
文摘Due to the complicated histopathological characteristics of clear-cell renal-cell carcinoma(ccRcC),non-invasive prognosis before operative treatment is crucial in selecting the appropriate treatment.A total of 126345 computerized tomography(cT)images from four independent patient cohorts were included for analysis in this study.We propose a V Bottieneck multi-resolution and focus-organ network(VB-MrFo-Net)using a cascade framework for deep learning analysis.The VB-MrFo-Net achieved better performance than VB-Net in tumor segmentation,with a Dice score of 0.87.The nuclear-grade prediction model performed best in the logistic regression classifier,with area under curve values from 0.782 to 0.746.Survival analysis revealed that our prediction model could significantly distinguish patients with high survival risk,with a hazard ratio(HR)of 2.49[95%confidence interval(CI):1.13-5.45,P=0.023]in the General cohort.Excellent performance had also been verified in the Cancer Genome Atlas cohort,the Clinical Proteomic Tumor Analysis Consortium cohort,and the Kidney Tumor Segmentation Challenge cohort,with HRs of 2.77(95%CI:1.58-4.84,P=0.0019),3.83(95%CI:1.22-11.96,P=0.029),and 2.80(95%CI:1.05-7.47,P=0.025),respectively.In conclusion,we propose a novel VB-MrFo-Net for the renal tumor segmentation and automatic diagnosis of ccRcc.The risk stratification model could accurately distinguish patients with high tumor grade and high survival risk based on non-invasive CT images before surgical treatments,which couid provide practical advicefordecidingtreatmentoptions.
文摘Renal-cell carcinoma(RCC)remains a leading cause of cancer-related mortality worldwide.Though newer therapeutic combinations of immune checkpoint inhibitors and targeted therapies have greatly improved outcomes,resistance to these therapies is becoming a challenge for long-term control.Mechanisms of resistance have been explored in a variety of solid tumors,including RCC.Based upon our review of the current literature on the mechanisms of resistance to immunotherapies for the management of metastatic clear-cell renal cell carcinomas(mccRCC),the ensuing conclusions have been made:The management of mccRCC has progressed substantially with the advent of checkpoint inhibitors and targeted oral therapies,alone and/or in combination.Nevertheless,innate or developed resistance to these therapies remains an ongoing challenge,particularly to immune checkpoint inhibitors(ICIs).Several of the known mechanisms of resistance have been well defined,but recent progression in cellular therapies helps to expand the armamentarium of potential combination options that may overcome these modes of resistance and improve long-term disease control and survival for an otherwise dismal disease.In the ensuing review and update of the literature on the mechanisms of resistance to immunotherapies in mccRCC,we have revisited the known resistance mechanisms of immunotherapies in metastatic clear-cell RCC and explored ongoing and future strategies to overcome them.
文摘Background:Vascular endothelial growth factor-targeted agents are standard treatments in advanced clear-cell renal cell carcinoma (ccRCC),but biomarkers of activity are lacking.The aim of this study was to investigate the association of Von Hippel-Lindau (VHL) gene status,vascular endothelial growth factor receptor (VEGFR) or stem cell factor receptor (KIT) expression,and their relationships with characteristics and clinical outcome of advanced ccRCC.Methods:A total of 59 patients who received targeted treatment with sunitinib or pazopanib were evaluated for determination at Cancer Hospital and Institute,Chinese Academy of Medical Sciences between January 2010 and November 2012.Paraffin-embedded tumor samples were collected and status of the VHL gene and expression of VEGFR and KIT were determined by VHL sequence analysis and immunohistochemistry.Clinical-pathological features were collected and efficacy such as response rate and Median progression-free survival (PFS) and ovcrall survival (OS) were calculated and then compared based on expression status.The Chi-square test,the KaplanMeier method,and the Lon-rank test were used for statistical analyses.Results:Of 59 patients,objective responses were observed in 28 patients (47.5%).The median PFS was 13.8 months and median OS was 39.9 months.There was an improved PFS in patients with the following clinical features:Male gender,number of metastatic sites 2 or less,VEGFR-2 positive or KIT positive.Eleven patients (18.6%) had evidence of VHL mutation,with an objective response rate of 45.5%,which showed no difference with patients with no VHL mutation (47.9%).VHL mutation status did not correlate with either overall response rate (P =0.938) or PFS (P =0.277).The PFS was 17.6 months and 22.2 months in VEGFR-2 positive patients and KIT positive patients,respectively,which was significantly longer than that of VEGFR-2 or KIT negative patients (P =0.026 and P =0.043).Conclusion:VHL mutation status could not predict the efficacy of sunitinib or pazopanib.Further investigation of VHL/VEGFR pathway components is needed.
文摘目的:透明细胞乳头状肾细胞肿瘤(clear cell papillary renal cell tumor,CCPRCT)是一种少见但重要的肾肿瘤类型,与其他肾细胞肿瘤具有类似的形态学特征,易导致误诊。本研究旨在探讨CCPRCT的临床病理特征、诊断及鉴别诊断要点,以提高其病理诊断的准确性。方法:收集15例CCPRCT患者,观察其临床及影像学特点,分析其镜下形态、免疫表型,并复习相关文献。结果:15例患者中,男10例,女5例,年龄为(54±17)岁,10例患者肿瘤位于左肾,5例患者肿瘤位于右肾。组织学上肿瘤均由增厚的纤维囊包裹,并局限于肾实质内;肿瘤细胞排列成乳头状、管状、囊状、腺泡及实性等结构;乳头由小到中等大小、透明细胞质的单层细胞组成,肿瘤均为世界卫生组织/国际泌尿病理学会(World Health Organization/International Society of Urological Pathology,WHO/ISUP)1级或2级;细胞核反极性分布,即核上移,靠近腔面,远离基底,类似鲨鱼牙齿排列。免疫组织化学染色显示:细胞角蛋白7、碳酸酐酶9(carbonic anhydrase 9,CA9)和高分子量细胞角蛋白(34βE12)均为阳性表达;α甲基酰基辅酶A消旋酶、CD117、转录因子E3均为阴性表达;CCPRCT中典型的CA9表现方式是“U型”着色,即腔缘不表达,基底和侧面表达。患者术后随访均未见复发或转移。结论:CCPRCT是一种惰性肾细胞肿瘤,预后好,临床可能存在过诊断,其形态学为特征性的核朝向腔缘的线性排列,特殊的免疫表型CA9呈“U型”阳性,可以与其他肾细胞肿瘤区分开来,但仍然需要积累更多患者来阐释其预后。
文摘术前预测透明细胞肾细胞癌(clear cell renal cell carcinoma,ccRCC)的分级可有效评估患者的预后并指导临床治疗,但实现精准预测是目前本领域内的一项重要问题。该研究首先确定最优建模的CT类型与网络层数,提出了一种基于改进残差网络的ccRCC的CT影像分级模型,具体包括:利用大卷积操作对图像进行原始特征提取,利用混合注意力模块通过计算特征图中当前空间和临近空间以及当前空间和远距离空间之间的信息交互获取更多有用的特征,使得原始图像特征图在通道维度与空间维度上进行自适应特征细化,利用四个深度卷积网络层提取图像深度特征,并利用改进通道注意力模块产生通道注意力特征图信息,提取更多通道上的交互信息。实验结果表明,增强CT实质期图像和34层残差网络最有利于分级预测模型的开发,所提出的模型的总体加权准确率、AUC、精度、召回率和F1分数分别为90.8%、0.897、90.5%、90.8%、90.9%,各项指标优于其他常见网络结构,因此,该模型在预测ccRCC的国际泌尿病理学学会(International Society of Urological Pathology,ISUP)分级方面有良好的效能,对患者的临床辅助诊断和预后治疗具有重要的理论指导意义。