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Clinicopathologic significance of hypoxia‐inducible factor 1α overexpression in gastric carcinomas
Author(s) -
Mizokami Ken,
Kakeji Yoshihiro,
Oda Shinya,
Irie Koji,
Yonemura Tomohiro,
Konishi Fumio,
Maehara Yoshihiko
Publication year - 2006
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.20568
Subject(s) - medicine , hypoxia (environmental) , gastric carcinoma , hypoxia inducible factors , gastric tumor , pathology , gastroenterology , cancer research , cancer , gene , oxygen , biochemistry , chemistry , organic chemistry
Abstract Background Hypoxia‐inducible factor 1α (HIF‐1α) plays a key role in responses to hypoxia and expression of HIF‐1α downstream genes leads to both an adapted metabolism and increased oxygen supply. We investigated the clinical significance of HIF‐1α expression in gastric carcinoma. Methods We examined HIF‐1α, vascular endothelial growth factor (VEGF), and insulin‐like growth factor‐2 (IGF‐2) expression patterns immunohistochemically in 126 specimens of gastric carcinoma. CD34 antigen levels were also examined by immunohistochemistry to determine microvessel density (MVD) within tumors and correlations between HIF‐1α expression, clinicopathological features, and survival were examined. Results HIF‐1α expression correlated with tumor size ( P < 0.005), depth of invasion ( P = 0.018), VEGF expression ( P = 0.03), and intra‐tumor MVD ( P < 0.005). IGF‐2 expression was more prevalent in HIF‐1α positive than in HIF‐1α negative tumors and the 5‐year survival rate was 58.4% for HIF‐1α positive patients and 81.5% for HIF‐1α negative patients ( P = 0.009). HIF‐1α expression is an independent prognostic factor in gastric carcinoma ( P = 0.032). Conclusions Overexpression of HIF‐1α in gastric carcinomas may upregulate its downstream gene products leading to VEGF‐mediated angiogenesis, and resulting in a poor prognosis for patients. J. Surg. Oncol. 2006;94:149–154. © 2006 Wiley‐Liss, Inc.