ArticleThe American journal of surgical pathology2011
Immunoexpression status and prognostic value of mTOR and hypoxia-induced pathway members in primary and metastatic clear cell renal cell carcinomas.
Article in The American journal of surgical pathology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Novel, emerging and provisional renal entities: The Genitourinary Pathology Society (GUPS) update on renal neoplasia.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2021Guideline
- A randomized phase 2 study of MK-2206 versus everolimus in refractory renal cell carcinoma.Annals of oncology : official journal of the European Society for Medical Oncology · 2017Trial
- The mechanism of the PI3K-AKT-mTOR signaling pathway in renal cell carcinoma: current developments and future prospects.Frontiers in oncology · 2026Review
- Article
- The role of hypoxia on prostate cancer progression and metastasis.Molecular biology reports · 2023Review
- Differential expression ofFrontiers in oncology · 2023Article
- Transcriptional and metabolic remodeling in clear cell renal cell carcinoma caused by ATF4 activation and the integrated stress response (ISR).Molecular carcinogenesis · 2022Article
- Do we need an updated classification of oncocytic renal tumors? : Emergence of low-grade oncocytic tumor (LOT) and eosinophilic vacuolated tumor (EVT) as novel renal entities.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2022Review
- Sirolimus increases the anti-cancer effect of Huai Er by regulating hypoxia inducible factor-1α-mediated glycolysis in hepatocellular carcinoma.World journal of gastroenterology · 2022Article
- GPNMB expression identifies TSC1/2/mTOR-associated and MiT family translocation-driven renal neoplasms.The Journal of pathology · 2022Article
- TSC loss is a clonal event in eosinophilic solid and cystic renal cell carcinoma: a multiregional tumor sampling study.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2022Article
- Eosinophilic vacuolated tumor (EVT) of kidney demonstrates sporadic TSC/MTOR mutations: next-generation sequencing multi-institutional study of 19 cases.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2022Article
- Validation of CT radiomics for prediction of distant metastasis after surgical resection in patients with clear cell renal cell carcinoma: exploring the underlying signaling pathways.European radiology · 2021Article
- Review of Prognostic Expression Markers for Clear Cell Renal Cell Carcinoma.Frontiers in oncology · 2021Review
- HIF1α is not a target of 14q deletion in clear cell renal cancer.Scientific reports · 2020Article
- mTOR and mTOR phosphorylation status in primary and metastatic renal cell carcinoma tissue: differential expression and clinical relevance.Journal of cancer research and clinical oncology · 2019Article
- MiR-216a exerts tumor-suppressing functions in renal cell carcinoma by targeting TLR4.American journal of cancer research · 2018Article
- Effect of Targeted Therapy With Pazopanib on Expression Levels of Transcription, Growth Factors and Components of AKT/m-TOR Signaling Pathway in Patients with Renal Cell CarcinomaAsian Pacific journal of cancer prevention : APJCP · 2017Article
- Toward personalized management in bladder cancer: the promise of novel molecular taxonomy.Virchows Archiv : an international journal of pathology · 2017Review
- Eukaryotic initiation factor 4E-binding protein 1 (4E-BP1): a master regulator of mRNA translation involved in tumorigenesis.Oncogene · 2016Review
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13 authors at 2 institutions in 1 country.
Funding
Abstract
The need for effective targeted therapies for renal cell carcinomas (RCCs) has fueled the interest for understanding molecular pathways involved in the oncogenesis of kidney tumors. Aiming to analyze the expression status and prognostic significance of mTOR and hypoxia-induced pathway members in patients with clear cell RCC (ccRCC), tissue microarrays were constructed from 135 primary and 41 metastatic ccRCCs. Immunoexpression levels were compared and correlated with clinicopathologic parameters and outcome. PTEN levels were significantly lower in primary and metastatic ccRCCs compared with benign tissues (P<0.001). Levels of phos-AKT, phos-S6, and 4E-binding protein-1 (4EBP1) were higher in metastatic ccRCC (P≤0.001). For phos-S6 and 4EBP1, levels were higher in primary ccRCC compared with benign tissues (P<0.001). c-MYC levels were higher in metastatic ccRCC (P<0.0001), and incremental p27 levels were observed in benign, primary ccRCC, and metastatic ccRCC (P<0.0001). HIF-1α levels were significantly higher in primary and metastatic ccRCCs compared with benign tissues (P<0.0001). In primary ccRCC, levels of all mTOR and hypoxia-induced pathway members were significantly associated with pT stage (P≤0.036), p27 levels with Fuhrman grade (P=0.031), and 4EBP1, p27, and HIF-1α levels with tumor size (P≤0.025). Tumor size, HIF-1α, and phos-S6 levels were associated with disease-specific survival (DSS) (P≤0.032) and tumor progression (P≤0.043). In conclusion, both mTOR and hypoxia-induced pathways were activated in primary and metastatic ccRCC. PTEN loss seems to be an early event during tumorigenesis. Tumor size, HIF-1α, and phos-S6 expression were found to be independent predictors of both DSS and tumor progression in primary ccRCC.
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