A preliminary study of microsatellite instability analysis in different genotypes of p53 codon 72 in breast invasive ductal carcinomas

  Abstract   Background: The polymorphic variants at codon 72 of the p53 gene, encoding either   proline or arginine at residue 72, produce marked change in the structure of p53.   From the evidence that the DNAmismatch repair system and p53 interact to maintain   genomic integrity, we hypothesized that the codon 72 variation may influence the   prevalence of microsatellite instability a feature of malignancies associated with   mismatch repair deficiency in breast invasive ductal carcinoma.   Methods: TP53 codon 72 genotypes were detected by PCR using specific primer   pairs for amplifying the Proline or the Arginine Alleles. Then, the frequencies of microsatellite instability (MSI) were analyzed in three genotypes of P53 codon 72 using   genomic DNAs from 120 specimens of breast ductal carcinomas by testing the   BAT-26 marker .   Results: From 120 specimens, 73(60.8%) was Arg/Arg, 31(25.8%) Arg/Pro and   16(13.3%) Pro/Pro. MSI analysis revealed that 24.2% of the tumors (29 patients) was   microsatellite instability-positive and 75.8% (91 patients) was microsatellite instability   -negative. The frequency of microsatellite instability in the Arginine/Arginine,   Arginine/ Proline and Proline/Proline genotypes were 14 (19.2%), 12 (38.7%) and 3   (18.8%) respectively. A significant difference in distribution of MSI was found for   the Arginine/ Proline genotype compared with (grouped) Arginine/Arginine and Proline/   Proline genotypes (P=0.028).   Conclusion: Our findings suggested that breast invasive ductal carcinomas arising   in individuals with p53 codon 72 heterozygosity (Arginine/Proline) may be preferentially   prone to microsatellite instability more than other genotypes.