RAS AND MYC ANALYSIS IN PRIMARY AND METASTATIC COLORECTAL CARCINOMAS - SPECIFIC RAS MUTATIONS ARE ASSOCIATED WITH DUKES-D STAGE AND MUCINOUS HISTOTYPE

Paired primary colorectal adenocarcinoma and normal frozen tissue samp les from 60 patients were prospectively studied to determine the frequ ency of point mutations in K-ras and the occurrence of structural alte rations in c-myc. Parallel investigations were performed on liver meta static specimens from 16 of the patients. 47% of the primary tumors pr esented point mutations in K-ras; 71% of these were in codon 12. Signi ficant associations were found between codon 13 ras mutations and Duke s' D stage (p<0.05), and between mutations in codon 12 and mucinous ty pe (p<0.01). The c-myc gene structure was altered in 5/60 cases (8%). In 4/16 cases, the K-ras gene status in the primary carcinoma and in t he metastatic tissue from the same patient was found to be different. Our results suggest that codon 13 I-as mutations may be associated wit h an increased invasive and metastatic potential, while codon 12 mutat ions may have a role in the mucinous differentiation pathway.