Tokunaga Yukihiko, Hosogi Hisahiro, Hoppou Toshitaka, Nakagami Mikio, Tokuka Atsuo, Ohsumi Kiyoshi
Department of Surgery, Maizuru Municipal Hospital, Kyoto, Japan.
Surgery. 2002 May;131(5):541-7. doi: 10.1067/msy.2002.123804.
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.
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.
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.
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.
胸苷磷酸化酶（TP）是激活5-氟尿嘧啶及其衍生物的关键酶，与血小板衍生的内皮细胞生长因子相同。在结直肠癌（CRC）中，既往评估TP表达与临床病理特征之间关系的研究结果并不一致。这些研究使用的单克隆抗体654-1对CRC细胞的染色较弱。现在，一种比654-1更敏感的新型单克隆抗体1C6-203已可获得。
本研究纳入了80例CRC患者，其肿瘤分期为II至IV期，并在我院接受了根治性手术切除。采用1C6-203免疫组织化学染色评估CRC中的TP表达。评估TP表达与可能影响患者预后的临床病理变量之间的关系。采用Kaplan-Meier法计算生存曲线，并用对数秩检验评估差异。在单因素和多因素生存分析中使用Cox比例风险模型。
TP表达与组织学分化进展（P = 0.025）、淋巴结转移（P = 0.083）、淋巴管浸润（P = 0.049）、静脉浸润（P = 0.042）和癌症分期（P = 0.002）呈正相关。TP阴性患者术后生存率高于TP阳性患者（P = 0.0041）。单因素分析显示，TP表达患者的总体死亡风险比为6.24（P = 0.013）。多因素分析显示，在调整其他临床病理变量后，TP是一个显著的预后因素。
使用新型高敏TP单克隆抗体，本研究结果表明TP表达与CRC进展和侵袭相关，且与CRC术后患者的不良预后密切相关。此外，TP表达是CRC患者的独立预后因素。
