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


CONCLUSIONS
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.
Popat
Sanjay
S
Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, SM2 5NG, UK. sanjay.popat@icr.ac.uk
Wort
Richard
R
Houlston
Richard S
RS
D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D004260:DNA Repair; D019008:Drug Resistance, Neoplasm; D006801:Humans; D018895:Microsatellite Repeats; D009154:Mutation; D010641:Phenotype; D011379:Prognosis; D013940:Thymidylate Synthase / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; D013940:Thymidylate Synthase