A prospective, blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of colorectal cancer.

Abstract

BACKGROUND:

Despite previous studies, uncertainty has persisted about the role of thymidylate synthase (TS) and p53 status as markers of prognosis in colorectal cancer (CRC).

PATIENTS AND METHODS:

A total of 967 patients accrued to a large adjuvant trial in CRC were included in a prospectively planned molecular substudy, and of them, 59% had rectal cancer and about 90% received adjuvant chemotherapy (either systemically or randomly allocated to intraportal 5-fluorouracil infusion or both). TS and p53 status were determined, blinded to any clinical data, by immunohistochemistry using a validated polyclonal antibody or the DO-7 clone, respectively, and their relationships with overall survival were examined.

RESULTS:

High TS expression was observed in 58% and overexpression of p53 in 60% of tumours. TS expression correlated with tumour stage, and p53 overexpression, with rectal cancers. There was no evidence that either marker was significantly associated with survival by either univariate (TS hazard ratio (HR) = 0.94, 95% CI 0.76-1.18 and P = 0.6 and p53 HR = 0.98, 95% CI 0.78-1.23 and P = 0.9) or multivariate analyses (TS HR = 0.99, 95% CI 0.79-1.25 and P = 0.9 and p53 HR = 0.98, 95% CI 0.78-1.23 and P = 0.8).

CONCLUSIONS:

Neither TS nor p53 expression has significant prognostic value in the adjuvant setting of CRC.

• Authors: S Popat, Z Chen, D Zhao, H Pan, N Hearle, I Chandler, Y Shao, W Aherne, Rs Houlston
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 17 Issue 12 Pg. 1810-7 (Dec 2006) ISSN: 0923-7534 [Print] England
• PMID: 16971666 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Biomarkers, Tumor
• Tumor Suppressor Protein p53
• Thymidylate Synthase
• Fluorouracil

Topics

• Antimetabolites, Antineoplastic (therapeutic use)
• Biomarkers, Tumor (metabolism)
• Chemotherapy, Adjuvant
• Colorectal Neoplasms (drug therapy, enzymology, metabolism)
• Female
• Fluorouracil (therapeutic use)
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Prognosis
• Prospective Studies
• Thymidylate Synthase (metabolism)
• Tumor Suppressor Protein p53 (metabolism)