Thymidylate synthase and p53 expression in primary tumor do not predict chemotherapy outcome in metastatic colorectal carcinoma.
BACKGROUND
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.


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).


CONCLUSIONS
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.
Berglund
Ake
A
Departments of Oncology, Radiology and Clinical Immunology, University of Uppsala, Akademiska Sjukhuset, Uppsala, Sweden. ake.berglund@onkologi.uu.se
Edler
David
D
Molin
Daniel
D
Nordlinder
Hans
H
Graf
Wilhelm
W
Glimelius
Bengt
B
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010166:Palliative Care; D016032:Randomized Controlled Trials as Topic; D013940:Thymidylate Synthase / Q000096:biosynthesis*; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D016159:Tumor Suppressor Protein p53; D013940:Thymidylate Synthase; D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate