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Eur J Cardiothorac Surg 2006;29:891-895
© 2006 Elsevier Science NL

Expression of hypoxia-inducible factor-1 alpha and its prognostic significance in small-sized adenocarcinomas of the lung

^a Second Department of Surgery, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
^b Department of Pathology, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
^c Department of Biochemistry, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan

Received 6 January 2006; received in revised form 9 March 2006; accepted 14 March 2006.

^_* Corresponding author. Address: Second Department of Surgery, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. Tel.: +81 92 801 1011; fax: +81 92 861 8271. (Email: md040004{at}cis.fukuoka-u.ac.jp).

Objective: To analyze the prognostic value of hypoxia-inducible factor-1 (HIF-1) alpha expression and its correlation with clinicopathologic variables and the expression of vascular endothelial growth factor-A and -C in patients with lung adenocarcinomas of small size. Methods: The expression of hypoxia-inducible factor-1 alpha was immunohistochemically determined in 78 cases of small-sized adenocarcinoma (maximum dimension 2 cm) using antibody against a recombinant protein corresponding to amino acids 575–780 of hypoxia-inducible factor-1 alpha. Data regarding patient survival, clinicopathologic factors, and immunohistochemical studies of vascular endothelial growth factors were also collected. Results: Strong expression of hypoxia-inducible factor-1 alpha was observed in 23 of 78 cases; absent or minimal expression was found in the localized bronchioloalveolar carcinomas. Strong expression of hypoxia-inducible factor-1 alpha was significantly higher in cases with vascular invasion, lymph node involvement, and vascular endothelial growth factor-A expression. The 5-year survival rate was 63.2% if expression of hypoxia-inducible factor-1 alpha was strong and 85.1% if expression was weak (p < 0.05). Conclusion: Immunohistochemical staining of HIF-1 alpha, along with examination of metastatic potential via vascular pathways, may be valid defining a subpopulation of patients with small-sized adenocarcinoma of the lung whose tumors have aggressive angiogenesis potential.

Key Words: Lung adenocarcinoma • Hypoxia-inducible factor-1 alpha • Vascular endothelial growth factor • Prognosis