胸苷酸合成酶的表达对结直肠癌患者预后的影响

目的　探讨结直肠癌组织中胸苷酸合成酶 (TS)的表达对患者预后的影响及与 5氟脲嘧啶 (5 Fu)类药物的相关性。方法　采用免疫组织化学染色的方法 (ABC法 )检测了 134例原发性结直肠癌患者 (ⅠB～Ⅳ期 )石蜡标本中的TS基因的表达情况。结果　 134例标本中TS基因表达的阳性率为 6 1 2 % (82 / 134) ,TS的表达与肿瘤分化程度、浸润深度、淋巴结转移与否及Dukes分期密切相关 (P <0 0 5 ) ,且TS表达阴性患者的 5年生存率 (5 7 6 9% )明显高于TS表达阳性者 (2 1 95 % ,P <0 0 0 1)。多因素分析显示 ,肿瘤的病理类型、浸润深度和TS表达状态 3者与生存率有相关性(P <0 0 5 ) ,其中TS的表达状态与患者 5年生存率关系最为密切 (P <0 0 0 0 1) ,相对危险系数为1 2 4 1。结论　TS表达水平的高低可能是判断结直肠癌患者预后的一个有效指标 ,同时对预测 5 Fu化疗效果具有一定的指导意义。

Relationship between expression of thymidylate synthase and colorectal carcinoma

OBJECTIVE: To study the relationship between the expression of thymidylate synthase (TS) gene and the prognosis of colorectal carcinoma and between the TS expression and the effect of 5-fluorouracil (5-Fu) on advanced colorectal carcinoma. METHODS: 134 formalin-fixed and paraffin-embedded specimens of colorectal carcinoma obtained during operation from 134 patients, 65 males and 69 females, aged 34 approximately 76 with an average age of 51 +/- 11, 16 with differentiated carcinoma and 118 with undifferentiated carcinoma, 4 with infiltration into mucous layer, 21 into submucous layer, 100 into muscular layer, and 5 into serous layer, 25 without lymphatic metastasis and 109 with lymphatic metastasis, 4 in stage IB, 15 in stage II, 90 in stage IIIA, and 27 in stage IIIB by Dukes staging, underwent immunohistochemistry (ABC methods) to determine the expression of TS. After operation all patients received chemotherapy with leucovorin and 5-Fu for 4 approximately 6 periods and were followed up for 9 approximately 72 months. RESULTS: Eighty-two specimens showed high TS expression and 52 showed low TS expression. The grade of TS expression was significantly correlated with four clinicopathologic variables: histological type, depth of invasion, lymphatic metastasis, and Dukes' stage (all P < 0.001). The 5-year survival rate for the low TS group was 57.69%, significantly lower than that of the high TS group (21.95%, P < 0.001). Multivariate analysis revealed that three variables (histological type, depth of infiltration, and TS grade) independently contributed to the survival rate (all P < 0.05), especially the TS grade (all P < 0.0001). The relative hazard ratio of TS grade was 1.241. CONCLUSION: The expression of TS is one of the important prognosis indicators of colorectal carcinoma. It is also a relatively reliable indicator of whether 5-Fu should be used in the treatment of patients with colorectal carcinoma.