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Kim and Park: Immunohistochemical Expression and Prognostic Value of VEGF, HIF-1α, EGFR in Non-Small Cell Lung Cancer
Original Article
Tuberculosis and Respiratory Diseases

Tuberculosis and Respiratory Diseases 2010; 68(1): 22-28.

Published online: 31 January 2010

DOI: https://doi.org/10.4046/trd.2010.68.1.22

Immunohistochemical Expression and Prognostic Value of VEGF, HIF-1α, EGFR in Non-Small Cell Lung Cancer

Myung Sook Kim, M.D., Sung Hak Park, M.D.

Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea.

Address for correspondence: Sung Hak Park, M.D. Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, 505, Banpo-dong, Seocho-gu, Seoul 137-701, Korea. Phone: 82-2-2258-2891, Fax: 82-2-599-3589, cmcpsh@catholic.ac.kr

Received 20 November 2009       Accepted 29 December 2009

Copyright © 2010. The Korean Academy of Tuberculosis and Respiratory Diseases. All rights reserved.

Abstract

Background

Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis. VEGF production is regulated by HIF-1α and EGFR. This study examined the relationship between the clinicopathological factors and VEGF, HIF-1α and EGFR protein overexpression, and evaluated their prognostic value in patients with a surgically resected non-small cell lung cancer (NSCLC).

Methods

Patients who underwent a surgical resection at Kangnam St. Mary's hospital were reviewed retrospectively. The core biopsy samples from 54 patients with NSCLC were assembled on a tissue microarray (TMA), and immunohistochemical staining for the VEGF, HIF-1α and EGFR proteins was performed. The overexpression of these proteins was evaluated in relation to age, gender, histology and staging by univariate analysis. The clinicopathological prognostic factors were analyzed.

Results

Multivariate analysis performed by Cox regression (odds ratio 2.8, 95% CI 1.0~8.2, p=0.046) revealed HIF-1α overexpression to be an unfavorable factor. There was no correlation between the overexpression of these proteins and the clinicopathological factors. VEGF showed a positive relationship with EGFR, but there was no statistical significance [p(χ2)=0.06].

Conclusion

HIF-1α overexpression predicts shorter survival in patients with a surgically resected NSCLC. Therefore, HIF-1α may be a poor prognostic factor in NSCLC.

Keywords: Carcinoma, Non-Small-Cell Lung, Immunohistochemistry, Prognosis

Figures and Tables

Figure 1
Immunohistochemical staining for VEGF, HIF-1α and EGFR of non-small cell lung cancer. Positive cells show brown cytoplasmic staining for VEGF (A, ×200), brown nuclear staining for HIF-1α (B, ×200), brown cell membrane staining for EGFR (C, ×200).
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Figure 2
Kaplan-Meier overall survival curves in patients with non-small cell lung cancer according to HIF-1α expression.
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Table 1
Clinicopathological factors of the 54 patients with non-small cell lung cancer
trd-68-22-i001
Table 2
Correlation between HIF-1α expression and clinicopathologic characteristics in 54 cases of non-small cell lung cancer
trd-68-22-i002
Table 3
Association between VEGF expression and EGFR or HIF-1α expression in 54 cases of non-small cell lung cancer
trd-68-22-i003
Table 4
Multivariate analysis of overall survival in 54 cases of non-small cell lung cancer
trd-68-22-i004

Multivariate analysis was conducted using Cox-proportional hazard model; results are showed as p-value.

CI: confidence interval; Adeno: adenocarcinoma; Squ: squamous cell carcinoma.

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