Expression of hypoxia-inducible factor-1 alpha and its prognostic significance in small-sized adenocarcinomas of the lung.
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 < or = 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).


CONCLUSIONS
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.
Enatsu
Sotarou
S
Second Department of Surgery, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. md040004@cis.fukuoka-u.ac.jp
Iwasaki
Akinori
A
Shirakusa
Takayuki
T
Hamasaki
Makoto
M
Nabeshima
Kazuki
K
Iwasaki
Hiroshi
H
Kuroki
Motomu
M
Kuroki
Masahide
M