Expression of Hypoxia-inducible Factor-1alpha in Non-small Cell Lung Cancer: Relationship to Prognosis and Tumor Biomarkers.
- Author:
Sung Rae CHO
1
;
Joung Hun BYUN
;
Jong In KIM
;
Bong Geun LEE
;
Bong Kwon CHUN
Author Information
1. Department of Thoracic and Cardiovascular Surgery, Kosin University College of Medicine, Korea. srcho@kosinmed.or.kr
- Publication Type:Original Article
- Keywords:
Carcinoma, non-small cell, lung;
Neoplasm marker;
Neoplasm proteins
- MeSH:
Anoxia;
Biomarkers*;
Biology;
Carcinoma, Non-Small-Cell Lung*;
Humans;
Immunohistochemistry;
Lung;
Lymph Nodes;
Multivariate Analysis;
Neoplasm Metastasis;
Neoplasm Proteins;
Pneumonectomy;
Prognosis*;
Signal Transduction;
Survival Rate;
Vascular Endothelial Growth Factor A
- From:The Korean Journal of Thoracic and Cardiovascular Surgery
2006;39(11):828-837
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1 (HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing O2 delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-1alpha has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-1alpha on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-1alpha expression on angiogenetic factors, relationship between the tumor proliferation and HIF-1alpha expression, interaction of HIF-1alpha expression and p53, and relationship between HIF-1alpha expression and clinico-pathological prognostic parameters were investigated. MATERIAL AND METHOD: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-1alpha, VEGF (vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex (ABC) immunohistochemistry. Relationship between the HIF-1alpha expression and VEGF, p53 overexpression and correlation between the HIF-1alpha expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. RESULT: HIF-1alpha expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma (40.7%). High HIF-1alpha expression was significantly associated with several pathological parameters, such as pathological TMN stage (p=0.004), pT stage (p=0.020), pN stage (p=0.029), and lymphovascular invasion (p=0.019). High HIF-1alpha expression was also significantly associated with VEGF immunoreactivity (p<0.001), and aberrant p53 expression (p=0.040). but was marginally associated with Ki-67 labeling index (p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-1alpha expression was worse than that of patients with low-expression (p=0.002). High HIF-1alpha expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. CONCLUSION: It is suggested that high HIF-1alpha expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-1alpha expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung ca
