Expression of vascular endothelial growth factor D is associated with lymph node metastasis in human colorectal carcinoma.
OBJECTIVE
Expression of vascular endothelial growth factor (VEGF)-D by tumors is associated with metastasis to lymph nodes in mice. However, there are few reports concerning the clinical significance of VEGF-D protein in human carcinoma.


METHODS
After confirming production of VEGF-D by eight colorectal carcinoma cell lines, we investigated relationships between the expression of VEGF-D protein, lymph node metastasis and postoperative survival in 83 colorectal carcinoma patients. mRNA levels in cell lines were evaluated using the real-time reverse transcriptase-polymerase chain reaction, and protein was detected by Western blotting in cell lines and by immunohistochemistry in resected tissues using an antibody recognizing the processed form of the molecule.


RESULTS
Immunohistochemistry showed VEGF-D-positive staining in 26 of the 83 carcinomas (31%). There was a significant relationship between the presence of VEGF-D protein and the incidence of lymph node metastasis (p < 0.01). Multivariate logistic regression analysis revealed that VEGF-D protein expression was an independent factor affecting lymph node metastasis (p < 0.01). Nonetheless, the presence or absence of VEGF-D protein had no significant impact on the survival of the patients (p = 0.15).


CONCLUSIONS
These results suggest that the expression of VEGF-D protein could be useful in predicting the nodal status of colorectal carcinoma patients.
Funaki
Hiroshi
H
Gastroenterologic Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan. funakih@mvj.biglobe.ne.jp
Nishimura
Genichi
G
Harada
Shin-Ichi
S
Ninomiya
Itasu
I
Terada
Itsuro
I
Fushida
Sachio
S
Tani
Takashi
T
Fujimura
Takashi
T
Kayahara
Masato
M
Shimizu
Koichi
K
Ohta
Tetsuo
T
Miwa
Koichi
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002277:Carcinoma / Q000737:chemistry* / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000473:pathology*; D016228:Endothelial Growth Factors / Q000032:analysis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000556:secondary; D016015:Logistic Models; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010534:Peritoneal Neoplasms / Q000556:secondary; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014407:Tumor Cells, Cultured; D042643:Vascular Endothelial Growth Factor D
D014408:Biomarkers, Tumor; D016228:Endothelial Growth Factors; D042643:Vascular Endothelial Growth Factor D