Mucinous colorectal cancers with chromosomal instability: a biologically distinct and aggressive subtype.

ABSTRACT

Colorectal cancers can progress through 2 pathways of genomic instability microsatellite instability (MSI) and chromosomal instability (CSI). We investigated the influence of CSI and MSI on clinicopathological features and survival of 35 patients affected by mucinous colorectal cancers (MCRC). MSI status was determined by PCR amplification using 5 standard markers. Evidence for CSI was gathered by identifying loss of heterozygosity (LOH) of 4 loci (2p, 5q, 17p, 18q). We defined "MSI-MCRC" as those that showed MSI-H, and "CSI-MCRC" as those that showed LOH at 1 or more of these sites but did not show MSI-H. Among 35 cases, 18 cases (51.4%) were CSI-MCRC, whereas 11 cases (31.4%) were MSI-MCRC. Significant differences were found between CSI-MCRC and MSI-MCRC regarding the following clinicopathological features tumor location (P=0.00026), lymph node metastasis (P=0.026), and TNM stage (P=0.026). Kaplan-Meier survival curves and log-rank analysis demonstrated that MSI-MCRC was associated with better prognosis than CSI-MCRC, although no significant difference was found (P=0.10). CSI-MCRC correlates more strongly with lymph node metastasis and advanced stage than MSI-MCRC. This indicates that CSI-MCRC is an aggressive subtype.