Clinicopathological, genetic, ultrastructural characterizations and prognostic factors of papillary renal cell carcinoma: New diagnostic and prognostic information

Yu, Wenjuan; Zhang, Wei; Jiang, Yu; Wang, Yuewei; Li, Yujun; Wang, Jigang; Sun, Lingling; Ran, Wenwen; Li, Hong

doi:10.1016/j.acthis.2012.10.009

Cited by 16 publications

(10 citation statements)

References 19 publications

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“…These experiments confirmed, the appearance of kidney structures including glomeruli, podocytes, glomeruli-associated basement membranes and proximal tubule with typical brush border-like structures. Interestingly, in c-met-mutated iPSC-derived kidney organoids, high numbers of glycogen granules were observed as previously reported in primary tumors 24 (Fig. 4c,f,g).…”

Section: Discussionsupporting

confidence: 86%

iPSC-derived Cancer Organoids Recapitulate Genomic and Phenotypic Alterations of c-met-mutated Hereditary Kidney Cancer

Desterke

Féraud

et al. 2019

Preprint

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Hereditary cancers with cancer-predisposing mutations represent unique models of human oncogenesis as a driving oncogenic event is present in germline, exposing the healthy member of a family to the occurrence of cancer. The study of the secondary events in a tissue-specific manner is now possible by the induced pluripotent stem cell (iPSC) technology offering the possibility to generate an unlimited source of cells that can be induced to differentiate towards a tissue at risk of malignant transformation. We report here for the first time, the generation of a c-met-mutated iPSC lines from the somatic cells of a patient with type 1 papillary renal cell carcinoma (PRCC). We demonstrate the feasibility of kidney differentiation with iPSC-derived organoids expressing markers of kidney progenitors with presence of tight junctions and brush borders in tubular structures at transmission electron microscopy. Importantly, c-met-mutated kidney organoids expressed PRCC markers both in vitro and in vivo in NSG mice. Gene expression profiling of c-met-mutated iPSCderived organoid structures showed striking molecular similarities with signatures found in a large cohort of PRCC patient samples and identified 11 common genes. Among these, BHLHE40 and KDM4C, well-known factors involved in PRCC pathogenesis, were expressed in c-met-mutated kidney organoids. This analysis applied to primary cancers with and without c-met mutation showed overexpression of the BHLHE40 and KDM4C only in the c-met-mutated PRCC tumors, as predicted by c-met-mutated organoid transcriptome. These data represent therefore the first proof of concept of the generation of "renal carcinoma in a dish" model using c-met-mutated iPSC-derived organoids, opening new perspectives for discovery of novel potentially predictive disease markers and novel drugs for future precision medicine strategies. 3

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Section: Discussionsupporting

confidence: 86%

iPSC-derived Cancer Organoids Recapitulate Genomic and Phenotypic Alterations of c-met-mutated Hereditary Kidney Cancer

Desterke

Féraud

et al. 2019

Preprint

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“…A screen of the titles and abstracts identified 50 papers eligible for the assessment of the prognostic value of CAIX status in patients with RCC. After carefully review of each of the 50 studies, certain studies were excluded for the following rationale: six studies evaluated CAIX status by enzyme-linked immunosorbent assay (ELISA) [23], [24], [25], [26], [27], [28]; five studies evaluated CAIX status by real-time-PCR [29], [30], [31], [32], [33]; one study was on the topic of a single nucleotide polymorphism in the CAIX gene [34]; fourteen studies did not report survival outcome on CAIX expression or survival outcome could not be extracted [17], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47]; and nine studies contained overlapping data with other studies by the same authors or institutions [48], [49], [50], [51], [52], [53], [54], [55], [56]. Thus, fifteen papers were included in our meta-analysis to evaluate the relationship between CAIX expression and prognosis in patients with renal cell carcinoma [16], [18], [19], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68].…”

Section: Resultsmentioning

confidence: 99%

Prognostic Value of Carbonic Anhydrase IX Immunohistochemical Expression in Renal Cell Carcinoma: A Meta-Analysis of the Literature

Zhao

Liao

et al. 2014

PLoS ONE

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BackgroundCarbonic anhydrase IX (CAIX) protein has been correlated with progression and survival in patients with renal cell carcinoma (RCC). The prognostic value of CAIX in RCC however, remains inconclusive according to published works. This study aimed to analyze CAIX as a biological marker to predict RCC patient prognosis.MethodsA literature search of the PubMed and Web of Knowledge databases was performed to retrieve original studies from their inception to December of 2013. Fifteen studies, collectively including a total of 2611 patients with renal cell carcinoma, were carefully reviewed. Standard meta-analysis methods were applied to evaluate the prognostic impact of CAIX expression on patient prognosis. The hazard ratio (HR) and its 95% confidence interval (CI) were recorded for the relationship between CAIX expression and survival, and the data were analyzed using Review Manager 5.2 software and Stata software 11.0.ResultsIn patients with RCC, low CAIX expression was associated with poor disease-specific survival (HR = 1.89, 95% CI: 1.20–2.98, P = 0.006), unfavorable progression-free survival (HR = 2.62, 95% CI: 1.14–6.05, P = 0.02) and worse overall survival (HR = 2.03, 95% CI: 1.28–3.21, P = 0.002). Furthermore, low CAIX expression was significantly associated with the presence of lymph node metastases (odds ratio (OR) = 0.31, 95% CI = 0.15–0.62, P = 0.0009) and distant metastases (OR = 0.66, 95% CI = 0.46–0.96, P = 0.03) and predicted a higher tumor grade (OR = 0.41, 95% CI = 0.31–0.54, P<0.00001).ConclusionsLow CAIX expression most likely indicates poor prognosis in RCC patients. Moreover, low CAIX expression was significantly associated with unfavorable clinicopathological factors. To strengthen our findings, further well-designed prospective studies should be conducted to investigate the role of CAIX expression in RCC.

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“…N of patients (type1/2) Type 1 Type 2 Yu et al [33] 56 pRCC (30/26) +17 −8; −18; −11 Sanders et al [35] 35 pRCC (21/14) AI 17q; 14q; 20q AI 9p Gunawan et al [38] 58 pRCC (35/23) +17p; +17q −8p; −11; −18; +1q Jiang et al [34] 25 pRCC (9/16) +7p; +17p 11.9 months with sunitinib vs 5.1 months with sorafenib, p < 0.0001) [58], although the study was not designed to allow a direct comparison between the two drugs. In summary this study, despite the small numbers of patients enrolled, described the activity of VEGF-inhibitors in patients with non-clear cell renal carcinoma, suggesting that patients with pRCC, as well as those with chromophobe RCC, may have prolonged PFS from sunitinib and sorafenib, but the rate of clinical responses is disappointedly low in pRCC.…”

Section: Studymentioning

confidence: 99%

“…Genetic analysis showed some chromosomal aberrations in all pRCC cases. As shown in Table 2, gains of chromosomes 7, 12, 17, 20 and loss of Y, 18, 9 are frequently found [33][34][35][36][37][38][39][40][41][42][43][44].…”

Section: Sporadic Papillary Renal Cell Carcinomamentioning

confidence: 99%

Papillary renal cell carcinoma: A review of the current therapeutic landscape

Courthod

Tucci

Maïo

et al. 2015

Critical Reviews in Oncology/Hematology

116

130

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Renal cell carcinoma (RCC) is the most common cancer of the kidney and accounts for 2-3% of all adult malignancies. Clear cell carcinoma represents the most common histologic subtype, while papillary Renal Cell Carcinoma (pRCC) accounts for 10-20% of all renal cell cancers. While the inactivation of VHL gene can be found in the majority of clear cell carcinomas, different molecular mechanisms are involved into pRCC biology. Mutations in the MET oncogene are an essential step into the pathogenesis of hereditary pRCC forms, but they can be found only in a small rate of sporadic cases. Several agents, including anti-VEGF drugs and mTOR inhibitors, are possible options in the treatment of advanced and metastatic pRCC, following the demonstration of efficacy obtained in clinical trials including all RCC histologic subtypes. However, data specifically obtained in the subgroup of patients affected by pRCC are limited and not conclusive. Several ongoing trials are evaluating the efficacy of targeted therapy in papillary form. However, more rationale approaches based on molecular studies would help improving the outcome of these patients. Among others, MET inhibitors and targeted immunotherapy are promising new strategies for hereditary and sporadic disease. This review summarizes current knowledge on pRCC tumorigenesis and discusses recent and ongoing clinical trials with new therapeutic agents.

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Clinicopathological, genetic, ultrastructural characterizations and prognostic factors of papillary renal cell carcinoma: New diagnostic and prognostic information

Cited by 16 publications

References 19 publications

iPSC-derived Cancer Organoids Recapitulate Genomic and Phenotypic Alterations of c-met-mutated Hereditary Kidney Cancer

iPSC-derived Cancer Organoids Recapitulate Genomic and Phenotypic Alterations of c-met-mutated Hereditary Kidney Cancer

Prognostic Value of Carbonic Anhydrase IX Immunohistochemical Expression in Renal Cell Carcinoma: A Meta-Analysis of the Literature

Papillary renal cell carcinoma: A review of the current therapeutic landscape

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