Mutations of the p53 gene and microsatellite inestability (MSI) as prognostic factors in metastatic colorectal cancer (CRC).

22088 Background: Several genetic changes have been described associated with CRC, but the prognostic significance of most of them remains controversial. We analysed the distribution and the association with survival of some molecular markers in CCR tissues.,From March-04 to June-05 73 patients were included with recent diagnosis of CRC: 53M/20F with a mean age of 70y (46-88). There were 25 rectal tumors (34%) and stage distribution was I:11, IIA:24, IIB:2, IIIA:3, IIIB:9, IIIC:8 and IV:16. During the anatomopathologic exam of the resected specimens, fresh samples were obtained (tumoral tissue and normal tissue), and they were stored in freezer vials at -86°C. In every sample all the following analysis were performed: LOH of the APC and DCC genes, MSI and Kras mutations using different biological techniques, and mutations of the p53 gene (exons 5 to 9) by sequence analysis.,LOH of DCC was found in 62% of the tumors, LOH of APC in 46% and MSI in 22% (MSI-LOW in 12 patients and MSI-HIGH in 4). Fifty one percent of the patients showed p53 mutations, mainly at the exons 5 (32%) and 8 (30%), and 38% carried a mutation in Kras (27 at the codon 12 and 1 at the codon 13). LOH of DCC was seen more frequently in older patients (p=0.045) and it showed associated with the presence of p53 mutations (p=0.005). In loco-regional stages (I-III), Kras was more frequently mutated in patients without node involvement (stages I-II vs III, p=0.012). In advanced disease, point mutations of p53 (p=0.031) and the abscence of MSI (p=0.022) were associated with a significant worse survival at multivariate analysis, even when clinical variables (age, gender, tumor location, palliative chemotherapy) were included in the model (p53: p=0.023; MSI: p=0.015).,In our cohort of patients, mutations of the p53 supressor gene and the absence of MSI in the primary tumor are independent prognostic factors in patients with ACRC at the moment of diagnosis. No significant financial relationships to disclose.