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Open Access Research article

Inter-relationship between microsatellite instability, thymidylate synthase expression, and p53 status in colorectal cancer: implications for chemoresistance

Sanjay Popat*, Richard Wort and Richard S Houlston

Author Affiliations

Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, SM2 5NG, UK

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BMC Cancer 2006, 6:150  doi:10.1186/1471-2407-6-150

Published: 5 June 2006

Abstract

Background

Studies indicate that thymidylate synthase (TS) expression, p53 and mismatch repair status have potential to influence colorectal cancer (CRC) outcome. There is, however, little data on the inter-relationship between these three markers. We sought to investigate whether relationships exist between these markers that might contribute to CRC phenotypes.

Methods

Four hundred and forty-one stage I-III CRCs were investigated. p53 status and TS expression were assessed by standard immunohistochemistry methods. Mismatch repair status was determined by assessment of microsatellite instability (MSI) using radiolabelled microsatellite genotyping.

Results

244 tumours (55%) over-expressed p53, and 259 (58%) expressed high TS levels. 65 tumours (15%) had MSI. A significant relationship between p53 over-expression and high TS expression was observed (p = 0.01). This was independent of MSI status. A highly significant inverse relationship between MSI and p53 status was observed (p = 0.001). No relationship was seen between MSI status and TS expression (p = 0.59).

Conclusion

Relationships exist between p53 status and TS expression, and MSI and p53 status. These inter-relationships may contribute to the clinical phenotype of CRCs associated with each of the molecular markers. High TS expression is unlikely to account for the clinical behaviour of CRCs with MSI.