Integrative analysis of sarcomatoid clear-cell renal cell carcinomas reveals an immune subgroup.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4571-4571
Author(s):  
Gabriel G. Malouf ◽  
Ronan Flippot ◽  
Roger Mouawad ◽  
Hui Yao ◽  
Eva Comperat ◽  
...  
Keyword(s):  
Renal Cell ◽  
Clear Cell ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Cell Receptor ◽  
Integrative Analysis ◽  
Renal Cell Carcinomas ◽  
Fuhrman Grade ◽  
Whole Exome ◽  
Receptor Signaling Pathway

4571 Background: Integrative analysis of clear-cell renal cell carcinomas (ccRCC) has revealed four transcriptomic subgroups associated with distinct patients outcomes. Integrative analysis of sarcomatoid ccRCC which represent the most agressive forms of ccRCC remains unknown. Methods: We performed integrative analysis of sarcomatoid (n = 28) and Fuhrman grade IV ccRCC (n = 9) using whole-exome sequencing (n = 37), RNA-sequencing (n = 32), and DNA methylation profiling by Infinium 450K arrays (n = 31). Correlation with clinico-pathlogical tumor features and patients outcomes were performed. Results: The most frequent somatic mutations in sarcomatoid ccRCC were VHL (71%), PBRM1 (50%), SETD2 (21%), BAP1 (11%), and TP53 (11%). Hierarchical unsupervised clustering of gene expression revealed two transcriptomic subgroups C1 and C2 which do not differ in term of clinical features, presence of sarcomatoid dedifferentiation and patients outcomes. Furthermore, these clusters do not differ according to their genomic features ( VHL, PBRM1 and SETD2 mutations) or their mutational loads. Strikingly, C1 cluster was highly enriched for genes related to T cell receptor signaling pathway (p = 2.6x10-6) and adapative immunity (p = 8.5x10-5); in addition, the C1 « immune » subgroup was characterized by up-regulation of genes related to cell cycle. Conversely, C2 cluster revealed down-regulation of metabolic pathways (p = 7. 5x10-5). At the epigenetic level, methylome clustering revealed two distinct epi-clusters, epi-C1 (n = 10) and epi-C2 (n = 21); patients with tumors belonging to C2 epi-cluster displayed 9p loss and harbored inferior progression-free survival as compared to those in C1 epi-cluster (11 months versus NR ; P = 0.02); of note, this was independent of clinico-pathological tumor features and transcriptomic classification. Conclusions: Our data suggest that genetic and epigenetic landscapes of sarcomatoid ccRCC might not differ from grade IV ccRCC. In addition, we discovered an immune sarcomatoid ccRCC cluster. This finding provides a rationale for use of immune checkpoint inhibitors in sarcomatoid ccRCC.

scholarly journals Clear Cell Papillary Renal Cell Carcinoma: A Potential Mimic of Conventional Clear Cell Renal Carcinoma on Core Biopsy

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Heath Liddell ◽  
Anton Mare ◽  
Sean Heywood ◽  
Genevieve Bennett ◽  
Hin Fan Chan
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Core Biopsy ◽  
Clear Cell ◽  
Incidental Finding ◽  
Papillary Renal Cell Carcinoma ◽  
Renal Cell Carcinomas ◽  
Fuhrman Grade ◽  
Stage Renal Disease

Clear cell papillary renal cell carcinoma (CCP-RCC) is a recently described, relatively uncommon variant of renal cell carcinoma (RCC) with a reported incidence of 4.1%. Thought to only arise in those with end stage renal disease, CCP-RCC is increasingly identified in those without renal impairment. CCP-RCCs have unique morphologic, genetic, and immunohistochemical features distinguishing them from both conventional clear cell renal cell carcinomas and papillary renal cell carcinomas. Immunohistochemically, these tumors are positive for CK7 and negative for CD10 and racemase. This is in contrast to conventional cell renal cell carcinomas (CK7 negative, CD10 positive) and papillary cell carcinomas (CK7, CD10, and racemase positive). These tumours appear to be indolent in nature, with no current documented cases of metastatic spread. We present the case of a 42-year-old female who presented with an incidental finding of a renal mass that on a core biopsy was reported as clear cell carcinoma, Fuhrman grade 1. She subsequently underwent a radical nephrectomy and further histological examination revealed the tumor to be a clear cell papillary renal cell carcinoma, Fuhrman grade 1.

scholarly journals Synchronous Brain Metastases as a Poor Prognosis Factor in Clear Cell Renal Carcinoma: A Strong Argument for Systematic Brain Screening

2021 ◽  
Author(s):  
Valentine Ruste ◽  
Marie-Pierre Sunyach ◽  
Ronan Tanguy ◽  
Emmanuel Jouanneau ◽  
Camille Schiffler ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Cell Renal Cell Carcinoma ◽  
Strong Argument ◽  
Poor Prognostic Factor ◽  
Fuhrman Grade

Abstract PurposeBrain metastases (BM) usually represent a poor prognostic factor in solid tumors. About 10% of patients with renal cancer (RCC) will present BM. Local therapies such as stereotactic radiotherapy (SRT), whole brain radiotherapy (WBRT), and surgery are used to achieve brain control. We compared survival between patients with synchronous BM (SynBM group) and metachronous BM (MetaBM group). MethodsIt is a retrospective study of patients with clear cell renal cell carcinoma (ccRCC) and BM treated with TKI between 2005 and 2019 at the Centre Léon Bérard in Lyon. We collected prognostic factors: The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk score, the TNM stage, the histological subtypes and the Fuhrman grade. Overall survival (OS) was defined from diagnosis of metastatic ccRCC to death. Brain progression-free survival (B-PFS) was defined from focal brain therapy to brain progression or death.Results99 patients were analyzed, 44 in the SynBM group and 55 in the MetaBM group. OS in the MetaBM group was 49.4 months versus 19.6 months in the SynBM group, p=0.0002. The median time from diagnosis of metastasic disease to apparition of BM in the MetaBM group was 22.9 months (4.3; 125.7). SRT was used for 101 lesions (66.4%), WBRT for 25 patients (16.4%), surgery for 21 lesions (13.8%), surgery followed by radiation for 5 lesions (3.3%). B-PFS for all patients was 7 months (IC95% [5.0-10.5]). ConclusionsSurvival of patients with synchronous BM is inferior to that of patients with metachronous BM. Outcome is poor in both cases after diagnosis of BM. Brain screening should be encouraged at time of diagnosis of metastatis in ccRCC.

scholarly journals External Validation of the Prognostic Value of an Immune-Associated Gene Panel for Clear Cell Renal Cell Carcinomas

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhiwen Xie ◽  
Lei Wu ◽  
Shan Hua ◽  
Yongqing Zhang ◽  
Fei Shi ◽  
...  
Keyword(s):  
Renal Cell ◽  
Prognostic Value ◽  
Cox Regression ◽  
Clear Cell ◽  
Checkpoint Inhibitors ◽  
External Validation ◽  
Gene Panel ◽  
Gene Set Enrichment Analysis ◽  
Immune Gene ◽  
Renal Cell Carcinomas

Clear cell renal cell carcinomas (ccRCCs) are highly immune infiltrates, and many of them respond to immunotherapy with checkpoint inhibitors including anti-PD-L1 or anti-PD1 agents. However, the effect of immune genes on clinical outcomes in ccRCCs has not been fully studied. Here, we show in this study that an immune-associated gene panel has a prognostic value for clear cell renal cell carcinomas. We performed single-sample gene set enrichment analysis (ssGSEA) and cell type identification by estimating subsets of RNA transcripts (CIBERSORT) algorithms on patient-matched normal renal and RCC tissues to characterize two immunophenotypes and immunological characteristic subpopulations. Furthermore, LASSO Cox regression was applied to develop a novel prognosis-associated model for ccRCC patients based on an immune-gene panel. The results were verified by the Gene Expression Omnibus (GEO) dataset and coordinated with the clinicopathological characteristics of ccRCCs, along with genomic signatures. Finally, based on the above perspectives, we generated a nomogram with a high prognostic efficiency for ccRCC patients. Overall, this study offers a unique perspective that can contribute to improving the accuracy of prognosis prediction and treatment with immunotherapy.

Non–Clear Cell Renal Cell Carcinomas: From Shadow to Light

2018 ◽  
Vol 36 (36) ◽  
pp. 3624-3631 ◽  
Author(s):  
Laurence Albiges ◽  
Ronan Flippot ◽  
Nathalie Rioux-Leclercq ◽  
Toni K. Choueiri
Keyword(s):  
Cell Cycle ◽  
Renal Cell ◽  
Clear Cell ◽  
Checkpoint Inhibitors ◽  
Expression Profiles ◽  
Collecting Duct ◽  
Genomic Analysis ◽  
Renal Cell Carcinomas ◽  
Pathologic Features ◽  
Clear Cell Rccs

Non–clear cell renal cell carcinomas (RCCs) account for up to 25% of kidney cancers and encompass distinct diseases with distinct pathologic features, different molecular alterations, and various patterns of response to systemic therapies. Recent advances in molecular biology and large collaborative efforts helped to better define the oncogenic mechanisms at play in papillary, chromophobe, collecting duct, medullary, translocation, and sarcomatoid RCCs. Papillary RCCs are divided into several subsets of tumors characterized by distinct gene expression profiles, chromatin remodeling genes, cell cycle changes, and alterations of the MET pathway. Chromophobe RCC genomic analysis revealed mostly metabolic pathway alterations with mitochondrial dysfunctions. Translocation RCCs are characterized by MITF fusions and wide genomic reprogramming. Collecting duct carcinomas are distinct entities from upper tract urothelial carcinomas associated with high T-cell infiltration and metabolic alterations. Medullary RCCs present alterations of the INI1 gene and rhabdoid features at pathologic analysis. Finally, sarcomatoid RCCs represent sarcomatoid differentiation for any subsets of RCCs with specific alterations associated with mesenchymal dedifferentiation. From the standpoint of systemic therapy, more than a decade of using VEGF and mTOR inhibitors showed that they generally had limited efficacy in non–clear cell RCCs compared with clear cell RCCs. MET inhibitors are actively being developed for papillary RCC with a specific focus on MET-driven tumors. Other strategies under investigation include CDK4/6 inhibitors in tumors with cell cycle alterations and EZH2 inhibitors in RCCs with INI1 loss. The emergence of immune checkpoint inhibitors and combination strategies enlarges the spectrum of investigational treatments. Better understanding of driver and passenger alterations and better patient stratification along with dedicated clinical networks will be key to improving the management of these rare tumors.

scholarly journals Nuclear and cytosolic pS727-STAT3 levels correlate with overall survival of patients affected by clear cell renal cell carcinoma (ccRCC)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jazmine Arévalo ◽  
David Lorente ◽  
Enrique Trilla ◽  
María Teresa Salcedo ◽  
Juan Morote ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Independent Manner ◽  
Fuhrman Grade ◽  
Transcription 3 ◽  
Aggressive Subtype

AbstractClear cell renal cell carcinoma (ccRCC) is the most frequent and aggressive subtype of renal carcinoma. So far, the basis of its oncogenesis remains unclear resulting in a deficiency of usable and reliable biomarkers for its clinical management. Previously, we showed that nuclear expression of the signal transducer and activator of transcription 3 (STAT3), phosphorylated at its serine 727 (pS727), was inversely proportional to the overall survival of ccRCC patients. Therefore, in the present study, we validated the value of pS727-STAT3 as a clinically relevant biomarker in ccRCC. This work is a retrospective study on 82 ccRCC patients treated with nephrectomy and followed-up for 10 years. Immunohistochemical expression of pS727-STAT3 was analyzed on a tissue microarray and nuclear and cytosolic levels were correlated with clinical outcome of patients. Our results showed that pS727-STAT3 levels, whether in the nucleus (p = 0.002; 95% CI 1.004–1.026) or the cytosol (p = 0.040; 95% CI 1.003–1.042), significantly correlate with patients’ survival in an independent-manner of clinicopathological features (Fuhrman grade, risk group, and tumor size). Moreover, we report that patients with high pS727-STAT3 levels who undergone adjuvant therapy exhibited a significant stabilization of the disease (~ 20 months), indicating that pS727-STAT3 can pinpoint a subset of patients susceptible to respond well to treatment. In summary, we demonstrated that high pS727-STAT3 levels (regardless of their cellular location) correlate with low overall survival of ccRCC patients, and we suggested the use of pS727-STAT3 as a prognostic biomarker to select patients for adjuvant treatment to increase their survival.

scholarly journals PD14-07 DIFFERENTIATION BETWEEN CLEAR CELL RENAL CELL CARCINOMAS AND ONCOCYTOMAS USING TEXTURE ANALYSIS OF CT IMAGES

2016 ◽  
Vol 195 (4S) ◽  
Author(s):  
Vinay Duddalwar ◽  
Xuejun Zhang ◽  
Darryl Hwang ◽  
Steven Cen ◽  
Felix Yap ◽  
...  
Keyword(s):  
Texture Analysis ◽  
Renal Cell ◽  
Clear Cell ◽  
Ct Images ◽  
Renal Cell Carcinomas

scholarly journals Obstructive sleep apnea and Fuhrman grade in patients with clear cell renal cell carcinoma treated surgically

2016 ◽  
Vol 35 (1) ◽  
pp. 51-56 ◽  
Author(s):  
Antoni Vilaseca ◽  
Daniel P. Nguyen ◽  
Emily A. Vertosick ◽  
Renato B. Corradi ◽  
Mireia Musquera ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Fuhrman Grade ◽  
Obstructive Sleep

The Diagnostic Accuracy of Percutaneous Renal Needle Core Biopsy and Its Potential Impact on the Clinical Management of Renal Cortical Neoplasms

2014 ◽  
Vol 138 (12) ◽  
pp. 1673-1679 ◽  
Author(s):  
Lan L. Gellert ◽  
Rohit Mehra ◽  
Ying-Bei Chen ◽  
Anuradha Gopalan ◽  
Samson W. Fine ◽  
...  
Keyword(s):  
Clinical Management ◽  
Renal Cell ◽  
Core Biopsy ◽  
Clear Cell ◽  
Renal Tumors ◽  
Low Grade ◽  
Renal Cell Carcinomas ◽  
Biopsy Diagnosis ◽  
Potential Impact ◽  
Renal Cortical Neoplasms

Context While biopsies are now increasingly being performed for the diagnosis of renal cortical neoplasms, the influence of the rendered pathological diagnoses on the clinical management is only rarely documented. Objectives To report our experience with consecutively performed renal biopsies and the potential impact of the diagnosis on subsequent clinical management. Design Material from needle biopsies performed consecutively at our institution between 2006 and 2011 was reviewed. The influence of the reported pathology results on the clinical management was determined from patient follow-up medical record review. Results In total, 218 percutaneous biopsies for renal masses were performed during this period. Among them, 181 (83%) yielded neoplastic tissue, including 81 clear cell renal cell carcinomas, 29 low-grade oncocytic neoplasms, 7 papillary renal cell carcinomas, 5 clear cell papillary renal cell carcinomas, 5 angiomyolipomas, and 14 urothelial carcinomas. Fourteen additional cases (6%) contained lesional material from clinically known nonneoplastic processes, for a total diagnostic yield of 89%. Twenty-three (11%) were nonrepresentative of lesional tissue. In 10 of these, repeat biopsies or resections established the diagnosis of renal tumors. Biopsy diagnosis was confirmed in 29 of 30 cases (97%) on subsequent nephrectomy. Following the biopsy diagnosis, there were significant differences in the clinical management; overall, 79% of clear cell renal cell carcinomas received therapeutic interventions, and 17% were put on active surveillance. In contrast, 77% of the benign or low-grade lesions were put on active surveillance. Conclusions Accurate and specific diagnosis can be rendered on renal core biopsy in most renal tumors, and the biopsy diagnosis can have a definitive role in their clinical management.

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