Document Detail


Immunoexpression status and prognostic value of mTOR and hypoxia-induced pathway members in primary and metastatic clear cell renal cell carcinomas.
MedLine Citation:
PMID:  21881486     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Luciana Schultz; Alcides Chaux; Roula Albadine; Jessica Hicks; Jenny J Kim; Angelo M De Marzo; Mohamad E Allaf; Michael A Carducci; Ronald Rodriguez; Hans-Joerg Hammers; Pedram Argani; Victor E Reuter; George J Netto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of surgical pathology     Volume:  35     ISSN:  1532-0979     ISO Abbreviation:  Am. J. Surg. Pathol.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-21     Completed Date:  2011-11-10     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  7707904     Medline TA:  Am J Surg Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1549-56     Citation Subset:  IM    
Affiliation:
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
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MeSH Terms
Descriptor/Qualifier:
Academic Medical Centers
Adult
Aged
Aged, 80 and over
Carcinoma, Renal Cell / diagnosis*,  metabolism,  secondary
Cell Hypoxia
Female
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
Kidney Neoplasms / diagnosis*,  metabolism
Male
Middle Aged
Nephrectomy
PTEN Phosphohydrolase
Phosphorylation
Prognosis
Ribosomal Protein S6 / metabolism
TOR Serine-Threonine Kinases / metabolism*
Tissue Array Analysis
Tumor Markers, Biological / metabolism
Young Adult
Grant Support
ID/Acronym/Agency:
P50 CA058236/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/HIF1A protein, human; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Ribosomal Protein S6; 0/Tumor Markers, Biological; EC 2.7.1.1/MTOR protein, human; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 3.1.3.48/PTEN protein, human; EC 3.1.3.67/PTEN Phosphohydrolase
Comments/Corrections
Comment In:
J Urol. 2012 Feb;187(2):469   [PMID:  22237313 ]

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