Genetic instability, p53 and nm23 mutation and clinicopathological features in rectal carcinoma

Defective DNA mismatch repair proteins fail to correct replication errors (RERs). These defects may lead to secondary, mutation of oncogenes and tumor suppressor genes. Microsatellite instability might be a marker of such replication errors. Eighteen rectal tumors were examined to evaluate genetic instability, in sporadic rectal cancer by PCR. RERs were observed in 27.8% of the cases. No significant difference was noticed between RER+ and RER- patients as far as prognosis, clinicopathological features and p53 gene mutation are concerned. The incidence of nm23 gene mutation was the only statistically significant difference between the 2 groups. Three patients with only one altered microsatellite showed advanced tumor and nm23 gene mutation. Two cases with 5 altered microsatellites and nm23 gene mutated are disease-free: in one of them the p53 gene was also mutated. Probably more than one altered microsatellite is necessary to protect from the effects of secondary mutations.