2020
DOI: 10.1002/path.5532
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Abstract: Clear cell renal cell carcinoma (ccRCC) is the most common form of renal cancer. Due to inactivation of the von Hippel-Lindau tumour suppressor, the hypoxia-inducible transcription factors (HIFs) are constitutively activated in these tumours, resulting in a pseudo-hypoxic phenotype. The HIFs induce the expression of genes involved in angiogenesis and cell survival, but they also reset the cellular metabolism to protect cells from oxygen and nutrient deprivation. ccRCC tumours are highly vascularized and the cy… Show more

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Cited by 15 publications
(10 citation statements)
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“…However, they also suggested that this is due to increased vessel area and size, which contradicts our hypothesis. A very recent study reported by Nilsson et al [ 32 ] may also support our hypothesis: eosinophilic ccRCC (Figure 4E ) was significantly less vascularised (CD31 and ‘hallmark_angiogenesis’) despite its hypoxia status (‘hallmark_hypoxia’). Moreover, the gene ontology term ‘hallmark_EMT’ and immune cell infiltration (CD3 and CD45) were enriched in eosinophilic cells, suggesting that the eosinophilic tumour may be associated with the ccB‐assigned tumour in the non‐VHL‐HIF pathway.…”
Section: Discussionsupporting
confidence: 89%
See 1 more Smart Citation
“…However, they also suggested that this is due to increased vessel area and size, which contradicts our hypothesis. A very recent study reported by Nilsson et al [ 32 ] may also support our hypothesis: eosinophilic ccRCC (Figure 4E ) was significantly less vascularised (CD31 and ‘hallmark_angiogenesis’) despite its hypoxia status (‘hallmark_hypoxia’). Moreover, the gene ontology term ‘hallmark_EMT’ and immune cell infiltration (CD3 and CD45) were enriched in eosinophilic cells, suggesting that the eosinophilic tumour may be associated with the ccB‐assigned tumour in the non‐VHL‐HIF pathway.…”
Section: Discussionsupporting
confidence: 89%
“…The Cancer Genome Atlas (TCGA) report from 2018 [ 2 ] reported that TP53 and breast cancer type 1‐associated protein 1 ( BAP1 ) mutations were correlated to poor outcomes; therefore, we compared the prognostic significance of the IHC/histology‐based classifier with that of these IHC markers. The reliability of p53 and BAP1 IHC‐based assays for detecting mutations in these genes has been established previously [ 32 , 33 ]. Both p53 and BAP1 negativity was significantly correlated with decreased RFS rate, but neither marker was correlated with poor CSS rate (see supplementary material, Figure S4 A,B).…”
Section: Resultsmentioning
confidence: 99%
“…2 A recent report has demonstrated that eosinophilic features (ie, areas with granular, eosinophilic cytoplasm) were less vascularized but harbored abundant infiltration immune cells (ICs) as compared with clear cell areas. 3 However, the correlation of eosinophilic ccRCCs with the underlying mechanisms, or responsiveness to systemic therapy involving immune checkpoint blockades, has not been fully investigated. 3 Currently, there are many standard strategies with systemic agents for metastatic ccRCC such as tyrosine kinase inhibitors (TKIs), single or double immune checkpoint inhibitor(s) (ICIs), or a combination of TKIs plus ICIs.…”
Section: Introductionmentioning
confidence: 99%
“…3 However, the correlation of eosinophilic ccRCCs with the underlying mechanisms, or responsiveness to systemic therapy involving immune checkpoint blockades, has not been fully investigated. 3 Currently, there are many standard strategies with systemic agents for metastatic ccRCC such as tyrosine kinase inhibitors (TKIs), single or double immune checkpoint inhibitor(s) (ICIs), or a combination of TKIs plus ICIs. 4 According to guidelines, these agents are recommended based on the International Metastatic RCC Database Consortium (IMDC) risk criteria, which were developed in the TKI era.…”
Section: Introductionmentioning
confidence: 99%
“…Different types of cells are distributed in different parts of many tumors, including ccRCC. The heterogeneity of cell type may directly lead to the heterogeneity of metabolism in different parts of the same tumor; for example, the clear cells in ccRCC should respond to angiogenesis and glycolysis inhibitors, while eosinophilic components in ccRCC may benefit from mTOR or glutaminase inhibition [ 61 ]. Although the Riskscore model was based on the expression differences of metabolic genes, and the relationship between the Riskscore model and the prognosis was roughly in line with our prediction after verification, the relationship between our model and metabolic pathways was not the same as the actual changes in ccRCC metabolic patterns, indicating the metabolic complexity of different stages of ccRCC.…”
Section: Discussionmentioning
confidence: 99%