Upregulation of hypoxia inducible factor 1alpha mRNA is associated with elevated vascular endothelial growth factor expression and excessive angiogenesis and predicts a poor prognosis in gastric carcinoma.
OBJECTIVE
To investigate the implication of the hypoxia inducible factor HIF-1alpha mRNA in gastric carcinoma and its relation to the expression of vascular endothelial growth factor (VEGF) protein, tumor angiogenesis invasion/metastasis and the patient's survival.


METHODS
In situ hybridization was used to examine expression of HIF-1alpha mRNA, and immunohistochemical staining was used to examine expression of VEGF protein and CD34 in 118 specimens from patients with gastric carcinoma.


RESULTS
The positive rates of HIF-1alpha mRNA and VEGF protein were 49.15% and 55.92%, respectively. Positive expressions of HIF-1alpha and VEGF in stage T3-T4 tumors and those with vessel invasion, lymph node metastasis and distant metastasis were dramatically stronger than stage T1-T2 cases and those without vessel invasion, lymph node metastasis and distant metastasis. The mean microvascular density (MVD) in stage T3-T4 tumors and those with vessel invasion, lymph node metastasis and distant metastasis was significantly higher than stage T1-T2 tumors and those without vessel invasion, lymph node metastasis and distant metastasis. The mean MVD in tumors with positive HIF-1alpha and VEGF expression was significantly higher than that in tumors with negative HIF-1alpha and VEGF expression. The expression of HIF-1alpha was positively correlated with VEGF protein. There were positive correlations between MVD and expression of HIF-1alpha and VEGF. The mean survival time and the 5-year survival rate in cases with positive expression HIF-1alpha and VEGF and MVD value >or= 41.5/0.72 mm2 were significantly lower than those with negative expression of HIF-1alpha and VEGF and MVD value < 41.5/0.72 mm2.


CONCLUSIONS
Overexpression of HIF-1alpha is found in gastric carcinoma. HIF-1alpha may induce the angiogenesis in gastric carcinoma by upregulating the transcription of VEGF gene, and take part in tumor invasion and metastasis. They can be used as prognostic markers of gastric cancer in clinical practice.
Ma
Jie
J
Department of Pathology, Wenzhou Medical College, Wenzhou, Zhejiang Province, China. majie20052006@163.com
Zhang
Li
L
Ru
Guo-Qing
GQ
Zhao
Zhong-Sheng
ZS
Xu
Wen-Juan
WJ
D000230:Adenocarcinoma / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D018279:Carcinoma, Signet Ring Cell / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D009362:Neoplasm Metastasis / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D013270:Stomach / Q000473:pathology / Q000503:physiopathology; D013274:Stomach Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A