Prognostic significance of proliferative activity, DNA-ploidy, p53 and Ki-ras point mutations in colorectal liver metastases

Paired colorectal liver metastases (CLM) and normal tissue samples from a c onsecutive series of 36 patients were studied prospectively. MIB-1 expressi on was studied by immunohistochemistry on paraffin-embedded sections. DNA p loidy and S-phase fraction (SPF) measurements were performed by flow cytome try on frozen tissues. Mutations within the p53 (exons 5-8) and c-Ki-ras (c odons 12 and 13) genes were detected by PCR single-strand conformation poly morphism analysis followed by sequencing. A high correlation was observed b etween the MIB-1 LI and SPF value (rho=0.81; P<0.01). Moreover, p53 gene mu tations were associated with either high MIB-1 LI and high SPF. In univaria te analysis, SPF and MIB-1 levels were related to risk of death. The associ ation between overall survival and DNA-ploidy or p53 mutations did not reac h statistical significance, but a slightly better survival was observed for patients either with DNA-diploid tumours or without mutations (P=0.05 and P=0.06, respectively). SPF was shown by multivariate Cox model analysis to be an independent prognostic variable and thus it might be a useful prognos tic factor in patients with CLM.