Expression of HIF-2a in clear-cell renal cell carcinoma independently predicts overall survival

Autor: Konstantinos Gkagkalidis, Georgios Dimitriadis, Dorothea Kapoukranidou, Maria Mironidou-Tzouveleki, Spyridon Kampantais, Victoras Gourvas
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Oncology
medicine.medical_specialty
Kaplan-Meier Estimate
Kidney
Nephrectomy
Risk Assessment
Pathology and Forensic Medicine
03 medical and health sciences
0302 clinical medicine
Renal cell carcinoma
Internal medicine
Basic Helix-Loop-Helix Transcription Factors
Biomarkers
Tumor
Tumor Microenvironment
medicine
Humans
Prospective Studies
Carcinoma
Renal Cell
Molecular Biology
Aged
Neoplasm Staging
Tissue microarray
business.industry
Gene Expression Profiling
General Medicine
Middle Aged
Prognosis
medicine.disease
Molecular medicine
Kidney Neoplasms
Gene Expression Regulation
Neoplastic
Clear cell renal cell carcinoma
030104 developmental biology
medicine.anatomical_structure
Hypoxia-inducible factors
Tissue Array Analysis
030220 oncology & carcinogenesis
T-stage
Immunohistochemistry
Female
business
Follow-Up Studies
Zdroj: Medical Molecular Morphology. 53:229-237
ISSN: 1860-1499
1860-1480
DOI: 10.1007/s00795-020-00249-3
Popis: The purpose of this study is to evaluate the expression and the prognostic role of main factors, involved in the hypoxia pathway, in patients with clear-cell renal cell carcinoma (ccRCC). Immunohistochemical expression of Hypoxia inducible factors (HIF) HIF-1a, HIF-2a, prolyl hydroxylases PHD1, PHD2, PHD3, and factor inhibiting HIF (FIH) was assessed on a tissue microarray, containing tumour and corresponding normal kidney tissue from 66 patients underwent surgery for ccRCC. Expression levels were evaluated in relation to T stage, Fuhrman grade, cancer-specific, and overall survival (OS). Cytoplasmatic expression of HIF-2a was positively correlated with expression of HIF-1a (p = 0.011). HIF-1a expression was also positively correlated with PHD3 and FIH (p = 0.020 and p = 0.039). Expression of HIF-1a was associated with lower Fuhrman grade (p = 0.008), while HIF-2a overexpression with unfavourable grade (p = 0.026). PHD3 was significant downregulated (84.8%). Age, LDH, presence of necrosis, Fuhrman grade, T stage, and HIF-2a cytoplasmatic expression were significant associated with OS of patients in univariable analysis. In multivariable analysis, HIF-2a expression (p = 0.006) and T stage (p = 0.001) remained as the only independent predictors for overall survival. These results indicate that HIF-2a overexpression not only is inversely correlated with Fuhrman grade in ccRCC, but also represents a strong independent prognostic factor for a poor overall survival.
Databáze: OpenAIRE
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