SYNCHRONOUS COLON CARCINOMAS - MOLECULAR-GENETIC EVIDENCE FOR MULTICENTRICITY

Background: The synchronous presentation of multiple colonic adenocarc inomas is an unusual, but well-recognized event accounting for similar to 2-11% of these neoplasms. Synchronous tumors may have a different biology and prognosis than solitary tumors. Evidence based on measurem ent of DNA ploidy suggests that a significant percentage of synchronou s tumors have a common clonal origin, probably resulting from translum enal metastasis. Methods: Fifteen synchronous colorectal cancers (30 t umors) were examined for histologic differences as well as genetic mut ations, p53 gene abnormalities were detected by polymerase chain react ion (PCR) followed by single-strand conformation polymorphism analysis . Ki-ras mutations were detected by PCR followed by oligonucleotide-sp ecific hybridization. Results: p53 gene mutations were detected in 12 of 30 tumors. In only one case was the same p53 mutation present in bo th tumors from one patient, Similarly, Ki-ras mutations were observed in 9 of 30 tumors. Concordant Ki-ras mutations were observed in only o ne case, which was also concordant for p53 mutation. Conclusion: Becau se p53 and Ki-ras mutations tend to occur fairly early in tumor develo pment, it seems likely that cases discordant for p53 and Ki-ras mutati ons represent independently developing tumor foci. Taken together, the se findings strongly suggest that the great majority of synchronous co lonic adenocarcinomas arise as independent neoplasms and their worsene d prognosis is not a result of unusually early metastatic spread.