Clinicopathologic and Molecular Characteristics of Synchronous Colorectal Cancers: Heterogeneity of Clinical Outcome Depending on Microsatellite Instability Status of Individual Tumors

BACKGROUND: The contribution of chromosomal instability, microsatellite instability, and epigenetic instability to the development of synchronous colorectal carcinomas is controversial. OBJECTIVE: This study aimed to investigate the relative roles of microsatellite instability and epigenetic instability in the development of synchronous colorectal cancers. DESIGN: This was a retrospective study of medical records with histologic, immunohistochemical, and molecular examination of stored tissue samples. SETTING: The study took place at Seoul National University Hospital, Korea. PATIENTS: A total of 46 patients with synchronous colorectal cancers and 105 patients with solitary colorectal cancers were included. MAIN OUTCOME MEASURES: Clinicopathologic and molecular characteristics including microsatellite instability, mismatch repair gene expression, CpG island methylator phenotype, and mutation of KRAS and BRAF were analyzed. RESULTS: Patients with synchronous tumors were more likely to be men than those with solitary tumors and had a tendency toward colocalization of individual tumors in the left or right colon. MSI-deficient cancers were more frequent in synchronous than in solitary cancers. The frequencies of CpG island methylator phenotype-high and KRAS and BRAF mutations were not different between synchronous and solitary cancers. No differences between synchronous cancers and solitary cancers were observed in overall survival or progression-free survival. Within the synchronous cancer group, patients with individual tumors discordant for microsatellite instability status had the worst clinical outcome, whereas those with individual tumors concordant for microsatellite instability-deficient status had the best clinical outcome. LIMITATIONS: The study was limited by its retrospective nature. Molecular analysis was performed only on cancerous lesions. CONCLUSIONS: Our findings suggest that microsatellite instability plays a more important role than does epigenetic instability in the development of synchronous colorectal cancers, and that information regarding concordant or discordant microsatellite instability status between individual tumors might help to predict clinical outcome of synchronous colorectal cancers.