THE ROLE OF THYMIDYLATE SYNTHASE EXPRESSION IN PROGNOSIS AND OUTCOME OF ADJUVANT CHEMOTHERAPY IN PATIENTS WITH RECTAL-CANCER

Purpose: We assessed the prognostic importance of the level of thymidy late synthase (TS) expression in patients with primary rectal cancer a nd whether, for Dukes' B and C cancer patients, the benefit of chemoth erapy was associated with TS expression. Patients and Methods: The lev el of TS expression in the primary rectal cancers of 294 of 801 patien ts enrolled on protocol R-01 of the National Surgical Adjuvant Breast and Bowel Project (NSABP) was immuno histochemically assessed with the monoclonal antibody TS 106. Results: Forty-nine percent of patients w hose tumors had low TS levels (n = 91) were disease free at 5 years co mpared with 27% of patients with high levels of TS (n = 203; P <.0.1). 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 wets significantly associated with Dukes' stage (P <.01 ); patients with a more advanced Dukes' stage had a significantly high er level of TS. The level of TS expression remained prognostic for bot h disease-free survival (P <.01) and survival (P <.05) independent of Dukes' stage and other pathologic characteristics evaluated. Thirty-ei ght percent and 54% of patients with high TS levels (n = 71) were dise ase free and alive, respectively, after 5 years when created with chem otherapy, 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 patie nts with low TS levels. Conclusion: The expression of TS is an importa nt independent prognosticator of disease-free survival and survival in patients with rectal cancer. Adjuvant fluorouracil (5-FU)-based chemo therapy demonstrated significa nt improvement in disease-free and over all survival for patients with high TS levels. Prospective studies mea suring TS levels will be needed to understand further the role of TS a s a prognosticator of survival and chemotherapeutic benefit. (C) 1994 by American Society of Clinical Oncology.