Coexpression of VEGF-C and Cox-2 in human colorectal cancer and its association with lymph node metastasis.
OBJECTIVE
Several lines of experimental evidence indicated that over-expression of vascular endothelial growth factor-C and cyclooxygenase-2 genes promotes angiogenesis and lymphangiogenesis, both of which are essential for the growth and spreading of tumor cells. This study was designed to evaluate the coexpression of vascular endothelial growth factor-C and cyclooxygenase-2 in human colorectal carcinoma to determine their relationships and correlations with lymph node metastasis and prognosis.


METHODS
Tissue samples of primary tumors and metastatic lymph nodes from 150 patients undergoing intentionally curative surgical resections for colorectal adenocarcinoma were immunohistochemically examined for vascular endothelial growth factor-C, cyclooxygenase-2, and CD34 expressions. Then, we analyzed their relationships and correlations with clinicopathologic findings and patients' survival time.


RESULTS
The positivity rate of vascular endothelial growth factor-C and cyclooxygenase-2 in the primary tumor was 68 and 72.7 percent, respectively, and in the metastatic lymph nodes was 93.3 and 80 percent, respectively. A significant correlation was found between the expression scores of vascular endothelial growth factor-C and cyclooxygenase-2 (P < 0.0001), and both also were correlated to microvessels density and several clinicopathologic parameters, including primary tumor size, lymph node metastasis, lymphatic invasion, and TNM stage. Patients with vascular endothelial growth factor-C-positive and/or cyclooxygenase-2-positive tumors had a significant shorter survival time than those with negative tumors did. However, in a multivariate analysis, only cyclooxygenase-2 expression was recognized as an independent prognostic factor (P = 0.0412; relative risk ratio, 3.067; 95 percent confidence interval, 1.046-8.994).


CONCLUSIONS
These data show that in human colorectal carcinoma, vascular endothelial growth factor-C and cyclooxygenase-2 are coexpressed and significantly associated with lymph node metastasis and prognosis.
Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Labile Togba
LT
Soumaoro
Hiroyuki
H
Uetake
Yoko
Y
Takagi
Satoru
S
Iida
Tetsuro
T
Higuchi
Masamichi
M
Yasuno
Masayuki
M
Enomoto
Kenichi
K
Sugihara
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018952:Antigens, CD34 / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016019:Survival Analysis; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*
D018952:Antigens, CD34; D008565:Membrane Proteins; D042582:Vascular Endothelial Growth Factor C; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human