Johnston P G, Fisher E R, Rockette H E, Fisher B, Wolmark N, Drake J C, Chabner B A, Allegra C J
National Cancer Institute-Navy Medical Oncology Branch, National Cancer Institute, Bethesda, MD 20889.
J Clin Oncol. 1994 Dec;12(12):2640-7. doi: 10.1200/JCO.1994.12.12.2640.
We assessed the prognostic importance of the level of thymidylate synthase (TS) expression in patients with primary rectal cancer and whether, for Dukes' B and C cancer patients, the benefit of chemotherapy was associated with TS expression.
The level of TS expression in the primary rectal cancers of 294 of 801 patients enrolled on protocol R-01 of the National Surgical Adjuvant Breast and Bowel Project (NSABP) was immunohistochemically assessed with the monoclonal antibody TS 106.
Forty-nine percent of patients whose tumors had low TS levels (n = 91) were disease free at 5 years compared with 27% of patients with high levels of TS (n = 203; P < .01). Moreover, 60% of patients with low TS levels were alive after 5 years compared with 40% of patients with high TS levels (P < .01). The level of TS protein was significantly associated with Dukes' stage (P < .01); patients with a more advanced Dukes' stage had a significantly higher level of TS. The level of TS expression remained prognostic for both disease-free survival (P < .01) and survival (P < .05) independent of Dukes' stage and other pathologic characteristics evaluated. Thirty-eight percent and 54% of patients with high TS levels (n = 71) were disease free and alive, respectively, after 5 years when treated with chemotherapy, compared with 17% and 31%, respectively, of similar patients when treated with surgery alone (n = 64) (P < .01). No difference was noted in disease-free survival (P = .46) or survival (P = .43) in patients with low TS levels.
The expression of TS is an important independent prognosticator of disease-free survival and survival in patients with rectal cancer. Adjuvant fluorouracil (5-FU)-based chemotherapy demonstrated significant improvement in disease-free and overall survival for patients with high TS levels. Prospective studies measuring TS levels will be needed to understand further the role of TS as a prognosticator of survival and chemotherapeutic benefit.
我们评估了胸苷酸合成酶（TS）表达水平在原发性直肠癌患者中的预后重要性，以及对于Dukes B期和C期癌症患者，化疗的获益是否与TS表达相关。
采用单克隆抗体TS 106，通过免疫组织化学方法评估了参加国家外科辅助乳腺和肠道项目（NSABP）R - 01方案的801例患者中294例原发性直肠癌患者的TS表达水平。
肿瘤TS水平低的患者（n = 91）中有49%在5年后无疾病，而TS水平高的患者（n = 203）中这一比例为27%（P <.01）。此外，TS水平低的患者中有60%在5年后存活，而TS水平高的患者中这一比例为40%（P <.01）。TS蛋白水平与Dukes分期显著相关（P <.01）；Dukes分期越晚的患者TS水平显著越高。独立于Dukes分期和其他评估的病理特征，TS表达水平对无病生存期（P <.01）和生存期（P <.05）仍具有预后价值。TS水平高的患者（n = 71）在接受化疗后，5年后分别有38%无疾病和54%存活，而单纯接受手术的类似患者（n = 64）中这两个比例分别为17%和31%（P <.01）。TS水平低的患者在无病生存期（P =.46）或生存期（P =.43）方面未观察到差异。
TS表达是直肠癌患者无病生存期和生存期的重要独立预后指标。基于氟尿嘧啶（5 - FU）的辅助化疗对TS水平高的患者在无病生存期和总生存期方面有显著改善。需要进行前瞻性研究来进一步了解TS作为生存预后指标和化疗获益指标的作用。
