Abstract 3762: CIMP is common for right-sided colon sessile serrated polyps but not for colorectal adenomas
Authors: Burnett-Hartman Andrea N. , Newcomb Polly A. , Potter John D. , Mandelson Margaret T. , Zhu Lee-Ching , Upton Melissa P. , Wurscher Michelle A. , Makar Karen W. 
Published: June 2012

Background: Several pathways for colorectal cancer (CRC) have been described. The well-known adenoma-to-carcinoma pathway usually results in microsatellite stable tumors and accounts for about 75% of CRC. Less is established about the origins of microsatellite unstable (MSI) CRC. These tumors are more often in the right colon and commonly characterized as having a CpG Island Methylator Phenotype (CIMP).

Objective: We aimed to better understand precursors for MSI colorectal tumors by determining the correlation between CIMP-status and polyp type.

Methods: We conducted a case-case comparison of CIMP status among participants aged 24-79 of a colonoscopy-based study, who were diagnosed with colorectal adenomas or hyperplastic polyps (HPs). During colonoscopy, polyps were biopsied, fixed in paraffin, and H&E slides prepared. All participants underwent a standard pathology review to confirm the diagnosis, determine the percent of lesional tissue in the block, and classify each polyp as tubular adenoma, tubulovillous adenoma, HP (both goblet cell and microvesicular), sessile serrated polyp, or serrated adenoma. Medical records were abstracted to ascertain polyp location and size; tissue blocks from polyps at least 3 mm in diameter and containing at least 80% lesional tissue were selected for CIMP analyses. DNA methylation was quantified in 905 polyps by real-time PCR (MethyLight) using a validated CIMP marker panel (CACNA1G, IGF2, NEUROG1, RUNX3, SOCS1). ALU was used to monitor DNA quality. Of the 905 polyps tested, 752 (83%) had an ALU cycle threshold &lt;23, and thus appropriate for CIMP analyses.

Results: Of 434 adenomatous polyps, including 113 tubulovillous adenomas, only 2 (&lt;0.5%) were CIMP-positive, both tubulovillous adenomas. For HPs and other serrated polyps, 87 out of 318 (27%) were CIMP-positive. Among these, sessile serrated polyps had the highest proportion of CIMP positivity: 59 of 108 (55%), followed by serrated adenomas: 4 of 11 (37%), and hyperplastic polyps: 24 of 199 (12%). Polyp location was also associated with CIMP status. For HPs/other serrated polyps, 2 of 87 (2%) rectal polyps were CIMP positive, 10 of 75 (13%) left colon polyps were positive, and 75 of 155 (48%) right were positive.

Discussion: Until recently, sessile serrated polyps were classified as hyperplastic polyps and therefore, were thought to have little clinical significance. However, our investigation suggests that these polyps, like MSI CRC tumors, are commonly CIMP-positive. Adenomatous polyps, in contrast, were largely CIMP-negative. This finding supports other investigations suggesting MSI CRC is not likely to have an adenomatous precursor, and probably arises from serrated polyps. If confirmed by longitudinal studies, this will have important implications for CRC surveillance.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3762. doi:10.1158/1538-7445.AM2011-3762