Introduction: Thymidylate synthase (TS) and p53 expression have been reported to predict the results of palliative chemotherapy in advanced colorectal carcinoma (ACRC), but the knowledge is still limited and partly conflicting.
Patients and methods: One hundred and twenty-two patients with ACRC were treated with 5-fluorouracil (5-FU)-based therapy at the University Hospital in Uppsala, Sweden, in four different randomised phase III studies between 1989 and 1997. Fifty-nine (48%) of the patients were initially diagnosed with advanced disease. There were 32 (26%) complete or partial radiological responders. The paraffin-embedded tumours at primary diagnosis were retrospectively analysed with immunohistochemical techniques (IHC) for TS using the specific monoclonal antibody, TS 106, and for p53 with the mouse monoclonal antibody DO-7.
Results: All analyses were independently reviewed. High TS values were seen in 78% and p53 positivity in 60% of the tumours. None of the markers predicted the outcome of the later palliative treatment, either in terms of an objective response or survival. However, for the subgroup who initially had curative resection (Dukes' A-C), TS expression had prognostic information and significantly predicted time to recurrence (median for low TS tumours 30 months and for high TS tumours 11 months, p = 0.001).
Conclusion: Immunohistochemical investigation of TS and p53 of the primary tumour is not useful to predict the outcome of palliative chemotherapy in ACRC. Instead, TS can be regarded as a marker for prediction of time to recurrence.