Prognostic value of thymidine phosphorylase/platelet-derived endothelial cell growth factor in advanced colorectal cancer after surgery: evaluation with a new monoclonal antibody.
BACKGROUND
Thymidine phosphorylase (TP) is an essential enzyme for activation of 5-fluorouracil and its derivatives and identical to platelet-derived endothelial cell growth factor. In colorectal cancer (CRC), previous studies evaluating the relationship between TP expression and clinicopathologic features have yielded inconsistent results. These studies used monoclonal antibody 654-1, which stained CRC cells weakly. Now, a new monoclonal antibody, 1C6-203, more sensitive than 654-1, is available.


METHODS
This study included 80 patients whose CRCs were classified into stages II to IV and completely resected surgically in our institute. TP expression in CRC was evaluated by using immunohistochemical staining with 1C6-203. Relationships between TP expression and clinicopathologic variables that might have affected the patients' prognosis were evaluated. Survival curves were calculated with the Kaplan-Meier method, and differences were evaluated with log-rank test. Cox proportional hazards model was used in the univariate and multivariate survival analyses.


RESULTS
TP expression showed a positive correlation with advances in histologic differentiation (P =.025), lymph node metastasis (P =.083), lymphatic invasion (P =.049), venous invasion (P =.042), and cancer stage (P =.002). The patients' survival rates after surgery were higher (P =.0041) in those with negative TP than in those with positive TP. The overall estimated hazard ratio for death in patients with TP expression was 6.24 according to univariate analysis (P =.013). Multivariate analysis showed that TP was a significant prognostic factor adjusted for other clinicopathologic variables.


CONCLUSIONS
With a new highly sensitive monoclonal antibody to TP, the present results indicated that TP expression is associated with CRC progression and invasion and closely correlated with poor prognosis in postoperative CRC patients. Moreover, TP expression is an independent prognostic factor in CRC patients.
Tokunaga
Yukihiko
Y
Department of Surgery, Maizuru Municipal Hospital, Kyoto, Japan.
Hosogi
Hisahiro
H
Hoppou
Toshitaka
T
Nakagami
Mikio
M
Tokuka
Atsuo
A
Ohsumi
Kiyoshi
K
D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000401:mortality* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000401:mortality; D011379:Prognosis; D015996:Survival Rate; D013939:Thymidine Phosphorylase / Q000032:analysis*
D000911:Antibodies, Monoclonal; D013939:Thymidine Phosphorylase