[p53 mutations in sporadic colorectal cancers with microsatellite instability]

To study p53 mutation and its association with microsatellite instability (MI)/replication error (RER) in sporadic colorectal cancer.

Fifty five cases of sporadic colorectal cancer were analyzed for MI/RER by PCR-based silver staining or ABI377 sequencer at following seven separate microsatellite loci: BAT-26, D2S119, D2S123, D3S1293, D8S282, D13S160 and D18S58. p53 mutations at exon 5 - 8 were detected by direct sequencing and its overexpressions performed by immunohistochemistry.

p53 gene mutations were present in 38.2% (21/55) of the tumors and its overexpressions in 60% (33/55) with a concordance rate of 42%. MI or RER positive rate was 27.2% (15/55) or 14.5% (8/55). MI/RER + cancers showed a tendency of relatively high p53 total mutation and point mutation rates with 53.3% VS 32.5% and 53.3% VS 30% in MI group (P > 0.05) and with 62.5% VS 34% and 62.5% VS 30.2% (P > 0.05) in RER group respectively; but they had low protein expression rate with 46.7% VS 65% in MI group and 50% VS 62% in RER group (P > 0.05). There were no differences in p53 missense mutation rates and distributions at CpG sites with 40% VS 30% and 20% VS 12.5% (P > 0.05) between the two kinds of MI/RER tumors. Furthermore, each (CA)n microsatellite locus had no significant effect on p53 mutation.

No significant relationship is found between MI/RER and p53 mutation/overexpression in sporadic colorectal cancer. But MI/RER tumor tends to have relatively high p53 mutation and low overexpression rates. In addition, there exist no differences in p53 missense mutation rates and distributions at CpG sites between the two kinds of MI/RER tumors.