Expression of survivin in gastric cancer and its relationship with tumor angiogenesis.
OBJECTIVE
Survivin, a member of inhibitors of apoptosis, has been found in various human cancers. Its expression is associated with tumor progression and adverse outcome. Angiogenesis is an essential process for the primary tumor to grow and invade the adjacent normal structures. Angiogenic factors such as vascular endothelial growth factor induce survivin expression in endothelial cells. The current study was designed to investigate the possible role of survivin and vascular endothelial growth factor status for angiogenesis in human gastric cancer.


METHODS
In this study, we conducted an immunohistochemical investigation of survivin and vascular endothelial growth factor expression in 106 tissue samples obtained from gastric cancer patients undergoing surgical treatment. To assess tumor angiogenesis, microvessel density was counted by staining endothelial cells immunohistochemically using anti-CD34 monoclonal antibody.


RESULTS
The positive expression of survivin and vascular endothelial growth factor in gastric cancer tissues was demonstrated in 50.0 and 69.8% of cases, respectively. The expression of survivin did not associate with vascular endothelial growth factor expression. Expression of survivin was significantly associated with tumor size, depth of invasion, lymph node metastasis, tumor stage and poor survival (P=0.011, 0.004, 0.020, 0.002, 0.046, respectively). High microvessel density was significantly associated with lymph node metastasis and poor survival (P=0.006 and 0.017, respectively). The mean microvessel density value of survivin positive tumors was 87.4+/-34.4 and significantly higher than that of survivin negative tumors (P=0.016). The mean microvessel density value of vascular endothelial growth factor positive tumors was 98.7+/-37.0 and significantly higher than that of vascular endothelial growth factor negative tumors (P=0.001). A combined analysis of survivin and vascular endothelial growth factor status showed that the mean microvessel density value of both positive tumors was 103.7+/-33.1 and significantly higher than that of both negative tumors (P<0.001).


CONCLUSIONS
These results suggest that survivin may play an important role in carcinogenesis by stimulating tumor angiogenesis in human gastric cancer.
Lee
Gi-Hoon
GH
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
Joo
Young-Eun
YE
Koh
Yang-Seok
YS
Chung
Ik-Joo
IJ
Park
Young-Kyu
YK
Lee
Jae-Hyuk
JH
Kim
Hyun-Soo
HS
Choi
Sung-Kyu
SK
Rew
Jong-Sun
JS
Park
Chang-Soo
CS
Kim
Sei-Jong
SJ
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007723:Korea; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000378:metabolism; D000077022:Survivin; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism*
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D042442:Vascular Endothelial Growth Factors