Hypoxia-inducible factor-1alpha expression and angiogenesis in gastrointestinal stromal tumor of the stomach.
Hypoxia inducible factor (HIF)-1 is reported to transactivate expression of vascular endothelial growth factor (VEGF), which is an important angiogenic factor. The aim of this study was to elucidate the clinical significance of HIF-1alpha expression in gastrointestinal stromal tumors (GIST). Specimens obtained from 53 patients who underwent surgical resection for GIST of the stomach were used in this study. Specimens were examined immunohistochemically for HIF-1alpha, VEGF, and Ki-67 expression. Tumor microvessel density (MVD) was determined immunohistochemically with anti-CD31 antibody and was estimated by averaging the counts from three high-power fields in the area showing the greatest neovascularization. HIF-1alpha expression was detected in 17 (32.1%) of 53 lesions and was correlated significantly with tumor size, liver metastasis, VEGF expression, and MVD. Prognosis was significantly poorer in patients with tumors expressing HIF-1alpha than in patients with tumors lacking HIF-1alpha expression. HIF-1alpha may play a role in angiogenesis and tumor progression of GIST through regulation of VEGF.
Takahashi
Ryoji
R
Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan.
Tanaka
Shinji
S
Hiyama
Toru
T
Ito
Masanori
M
Kitadai
Yasuhiko
Y
Sumii
Masaharu
M
Haruma
Ken
K
Chayama
Kazuaki
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011379:Prognosis; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000378:metabolism*; D017154:Stromal Cells; D015996:Survival Rate; D014157:Transcription Factors / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019394:Ki-67 Antigen; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A