Differential Expression of Hypoxia Inducible Factor-1 alpha and Tumor Cell Proliferation Between Squamous Cell Carcinomas and Adenocarcinomas Among Operable Non-Small Cell Lung Carcinomas

Abstract

This study aimed to evaluate whether the elevated level of hypoxia-inducible factor-1 (HIF-1 ) correlated with histologic types, angiogenesis, tumor cell proliferation, and clinical parameters in common non-small cell lung carcinomas (NSCLCs). We performed immunohistochemical stains using paraffin-embedded tissue blocks from 84 cases of operable NSCLC [No. of squamous cell carcinoma (SCC), 45; No. of adenocarcinoma (AC), 39]. HIF-1 expression was related with histologic types (66.7% in SCCs vs 20.5% in ACs, p<0.001), but not with lymph node status, tumor stage, vascular endothelial growth factor expression, microvessel density (MVD), and proliferating cell nuclear antigen (PCNA) index (p>0.05, respectively). As for the histologic types, MVD and PCNA index were significantly higher in SCCs than in ACs (p=0.009 and p=0.016, respectively). Among HIF-1 positive carcinomas, MVD was significantly higher in HIF-1 positive SCCs than in HIF-1 positive ACs (p= 0.023). The overall survival curves were not associated with HIF-1 expression or any other histologic parameters (p>0.05). These findings suggest that HIF-1 expression in NSCLCs may play a differential role according to histologic types, but its prognostic significance is indeterminate.

High levels of carbonic anhydrase IX in tumour tissue and plasma are biomarkers of poor prognostic in patients with non-small cell lung cancer

“…However, there was no significant relationship between HIF-1a overexpression and survival of all NSCLC patients. Our findings are supported by those of Lee et al (2003) who showed no association between HIF-1a expression and overall survival in 84 NSCLC patients. In contrast to our results, other groups reported a significant relationship between HIF-1a expression and shorter survival (Swinson et al, 2004;Kim et al, 2005).…”

Erythropoietin and Erythropoietin Receptor Coexpression Is Associated with Poor Survival in Stage I Non–Small Cell Lung Cancer

“…This finding is at variance with previous reports (35), although the prognosis after resection of the various histologic subtypes is still a subject of debate (36,37). In the present series, a positive correlation was observed between squamous cell carcinoma histology and EPO-R expression, which can be compared with a previously described association between this histology and hypoxiainduced factor-1a expression (38). The effect of hypoxia and anemia on EPO-R/EPO expression in tumor cells has not been fully evaluated.…”

Expression and Significance of Hypoxia Inducible Factor-1α and Lysyl Oxidase in Non-small Cell Lung Cancer

“…However, association of HIF-1α with clinicopathological characteristics and prognosis is inconsistent. Previous studies reported that HIF-1α expression in NSCLC was marginally associated with histological types, T-stage and poor prognosis (Lee et al, 2003;Swinson et al, 2004). There are several possible reasons for the inconsistency.…”