Correlation of integrin beta3 mRNA and vascular endothelial growth factor protein expression profiles with the clinicopathological features and prognosis of gastric carcinoma.
OBJECTIVE
To investigate integrin beta3 mRNA and vascular endothelial growth factor (VEGF) protein expression in gastric carcinoma, and its correlation with microvascular density, growth-pattern, invasion, metastasis and prognosis.


METHODS
In situ hybridization(ISH) of integrin beta3 mRNA and immunohistochemistry of VEGF and CD34 protein were performed on samples from 118 patients with gastric cancer.


RESULTS
The positive rate of integrin beta3 mRNA in non-tumor gastric mucosa (20%) was significantly lower than that of the gastric cancer tissue (52.5%, c2 = 10.20, P < 0.01). In patients of infiltrating type, stage T(3)-T(4), vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the positive expression rates of integrin beta3 mRNA were significantly higher than those in patients of expanding type (P < 0.01), stage T(1)-T(2) (P < 0.01), non-vessel invasion (P < 0.01), without lymphatic metastasis (P < 0.01), without hepatic and peritoneal metastasis (P < 0.01), respectively. In patients of infiltrating type, stage T(3)-T(4), vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the positive expression rates of VEGF protein were significantly higher than those in patients of expanding type (P < 0.01), stage T(1)-T(2) (P < 0.01), non-vessel invasion (P < 0.01), without lymphatic metastasis (P < 0.01), without hepatic and peritoneal metastasis (P < 0.01), respectively. In patients of infiltrating type, stage T(3)-T(4), vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the mean MVD were significantly higher than those in patients of expanding type (P < 0.01), stage T(1)-T(2) (P < 0.01), non-vessel invasion (P < 0.01), without lymphatic metastasis (P < 0.01), without hepatic and peritoneal metastasis (P < 0.01), respectively. It was found that the positive expression rate of integrin beta3 mRNA was positively related to that of VEGF protein (P < 0.01) and MVD (P < 0.05), meanwhile the positive expression rate of VEGF protein was positively related to MVD (P < 0.05). The mean survival period in patients with positive expression of integrin beta3 mRNA and VEGF, and MVD > or = 54.9/mm(2) was significantly shorter than that in patients with negative expression of integrin beta3 mRNA (P < 0.05) and VEGF (P < 0.01), and MVD < 54.9/mm(2) (P < 0.01). Five-year survival rate in patients with positive expression of integrin beta3 mRNA and VEGF, and MVD > or = 54.9/mm(2) was significantly lower than those with negative expression of integrin beta3 mRNA (P < 0.05), VEGF (P < 0.05), and MVD < 54.9/mm(2) (P < 0.01).


CONCLUSIONS
Integrin beta3 and VEGF expression can synergistically enhance tumor angiogenesis, and may play a crucial role in invasion and metastasis of gastric carcinoma. Therefore, they may be prognostic biomarkers and novel molecular therapeutic targets.
Li
Shu-Guang
SG
Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang Province, China.
Ye
Zai-Yuan
ZY
Zhao
Zhong-Sheng
ZS
Tao
Hou-Quan
HQ
Wang
Yuan-Yu
YY
Niu
Chun-Yu
CY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D039661:Integrin beta3; D053208:Kaplan-Meier Estimate; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D011379:Prognosis; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D039661:Integrin beta3; D042461:Vascular Endothelial Growth Factor A