Clinicopathological characteristics of colorectal cancers with loss of imprinting of insulin-like growth factor 2.

Loss of imprinting (LOI), the biallelic expression of an imprinting gene, of insulin-like growth factor 2 (IGF2) has been reported to be associated with colorectal carcinogenesis because of its high prevalence in normal colorectal mucosa as well as cancerous tissue in patients with colorectal cancer. However, the characteristics of colorectal cancer associated with IGF2 LOI have not been clearly demonstrated. In this study, we investigated the IGF2 LOI status of tumor and normal mucosa in 255 consecutive patients with colorectal cancer. Of these, 95 were informative for IGF2 LOI, by direct sequencing of mRNA of IGF2. Regarding the LOI status in each patient, the prevalence of LOI in nontumorus normal mucosa was significantly higher in cases with LOI-positive cancer than in those with LOI-negative cancer (p < 0.001). Concerning the clinicopathological characteristics of LOI-positive cancer, the prevalence of poorly differentiated or mucinous carcinoma (p = 0.016) and of right-sided locations (p = 0.009) were significantly higher than those of LOI-negative cancer. Contrary to past reports that revealed a significant correlation between microsatellite instability (MSI) and IGF2 LOI in a relatively small series of noncohort patients, our study did not find a statistically significant difference in LOI-positive rate between MSI-positive and -negative cases. Our results suggested the presence of a particular type of colorectal cancer associated with the proximal colon and poor differentiation, but independent of MSI. These results may contribute to clarification of the mechanism of colorectal tumorigenesis and to determining an appropriate screening strategy for colorectal carcinoma.