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Ann Oncol. 2004 Jan;15(1):55-8.

Lack of correlation between immunohistochemical expression of E2F-1, thymidylate synthase expression and clinical response to 5-fluorouracil in advanced colorectal cancer.

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  • 1Division of Medical Oncology, University of Udine, P. le S. M. Misericordia, Udine, Italy.

Abstract

BACKGROUND:

The level of the enzyme thymidylate synthase (TS) is known to inversely correlate with the clinical activity of 5-fluorouracil (FU) in advanced colorectal cancer patients. Since the correlation is not very strong, we have retrospectively analyzed the expression of E2F-1 in tumor samples or metastases from 25 patients with advanced colorectal cancer, homogeneously treated with an FU-based regimen. E2F-1 is a transcription factor regulating the expression of TS along with other crucial DNA synthesis related enzymes.

MATERIALS AND METHODS:

E2F-1 expression was analyzed by immunohistochemistry using the anti-E2F-1 monoclonal antibody KH95, scoring 2000 cells/case. Expression of TS was evaluated by immunohistochemistry using a rabbit anti-human polyclonal antibody.

RESULTS:

The level of E2F-1 expression did not correlate with TS expression, although a trend for correlation between E2F-1 level and maximal tumor shrinkage was observed (r = 0.42; P = 0.054).

CONCLUSIONS:

In spite of previous reports demonstrating that E2F-1 quantified by rt-PCR and western blot correlates with TS and could be used as a predictor to select colorectal cancer patients more likely to respond to FU treatment, our data suggest that, under these experimental conditions, immunohistochemistry cannot be used for such selection.

PMID:
14679120
[PubMed - indexed for MEDLINE]
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