Prognostic implications of hypoxia-inducible factor-1α in epidermal growth factor receptor-negative non-small cell lung cancer.
Hypoxia-inducible factor (HIF)-1α is a regulatory subunit of HIF-1 that is stabilized and activated under hypoxic conditions. In non-small cell lung cancer (NSCLC), over-expression of HIF-1α has been associated with poor overall survival. However, there is conflicting data on the role of HIF-1α as a prognostic factor. Some studies have demonstrated close association between the HIF-1α signal pathways and epidermal growth factor receptors (EGFRs). We evaluated the prognostic significance of HIF-1α expression in 178 NSCLC patients using tissue microarray in the context of EGFR gene copy number and protein expression status. EGFR gene copy number was evaluated using fluorescent in situ hybridization (FISH), and EGFR protein expression was determined using immunohistochemistry (IHC). The difference in overall survival (OS) between HIF-1α-positive and HIF-1α-negative groups was statistically significant in patients with low EGFR gene copy number and negative EGFR expression (log-rank test, P = 0.03). In univariate and multivariate analyses, HIF-1α was a significant worse prognostic factor for OS in patients with low EGFR gene copy number and negative EGFR expression (hazard ratio = 2.992; 95% CI, 1.113-8.045; P = 0.03 in univariate analysis and hazard ratio = 8.127; 95% CI, 1.874-35.251; P < 0.01 in multivariate analysis). The results demonstrated that the prognostic significance of HIF-1α should be validated in the context of EGFR status in NSCLC patients, and the gene and protein status of EGFR and HIF-1α will be important to help select patients most likely to derive the greatest clinical benefit from EGFR or HIF-1α targeted therapies.
Park
Sanghui
S
Department of Pathology, Gil Medical Center, Gachon University of Medicine and Science, Namdong-gu, Guwol-dong, 1198 Incheon, Republic of Korea.
Ha
Seung Yeon
SY
Cho
Hyun Yee
HY
Chung
Dong Hae
DH
Kim
Na Rae
NR
Hong
Junshik
J
Cho
Eun Kyung
EK
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D018628:Gene Dosage; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D066246:ErbB Receptors