Abstract 3310: Association between molecular characteristics of serrated polyps and subsequent advanced colorectal neoplasia
Authors: Hua Xinwei , Newcomb Polly , Chubak Jessica , Malen Rachel , Ziebell Rebecca , Kamineni Aruna , Zhu Lee-Ching , Upton Melissa , Newman Hana , Hardikar Sheetal , Burnett-Hartman Andrea 
Published: August 2019

Abstract
Purpose: Molecular characteristics, including BRAF mutation, MLH1 methylation, and CpG island methylator phenotype (CIMP), help identify aggressive subtypes of colorectal cancer (CRC), but their role is unclear for precursor lesions, especially in serrated polyps. Hyperplastic polyps (HPs) are serrated polyps that were considered to have no malignant potential, but a subset of HPs has been reclassified as sessile serrated polyps/adenomas (SSP/As), and SSP/As are now considered CRC precursors. In this study, we evaluated the association between molecular markers of serrated polyps and subsequent advanced colorectal neoplasia.
Methods: Study subjects included Kaiser Permanente Washington members who were 20-75 years old, received an index colonoscopy between 1/1/98-12/31/07 with a diagnosis of HPs or SSP/As and were free of synchronous conventional adenomas, inflammatory bowel disease, familial CRC syndromes, and prior or prevalent CRC. All eligible participants received ≥1 subsequent endoscopy or a CRC diagnosis before 1/1/13. These subsequent endoscopy pathology reports and clinical biopsies were reviewed for advanced colorectal neoplasia, defined as CRC, conventional adenomas ≥10 mm, with ≥20% villous components, with high-grade dysplasia, or SSP/As with nuclear dysplasia. Incident CRC cases were also identified through linkage to the SEER registry. Polyps from index colonoscopies were assayed for BRAF mutation (V600E), MLH1 methylation, and CIMP (using an 8-marker panel). We used generalized estimating equations with a binomial distribution, logit link, and independent correlation structure to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for advanced colorectal neoplasia, comparing subgroups of serrated polyps with different molecular characteristics.
Results: We included 733 subsequent endoscopies among 553 individuals with index serrated polyps (420 HPs and 133 SSP/As). The prevalence of BRAF mutation, MLH1 methylation, and CIMP-high among index serrated polyps were 51%, 2%, and 4% respectively. Compared to those without MLH1 methylation, those with MLH1methylated serrated lesions were more likely to have advanced colorectal neoplasia at a subsequent endoscopy, but the association was not statistically significant (adjusted OR = 1.95; 95% CI: 0.46-8.35). When restricted to index SSP/As, we observed a stronger association with MLH1 methylation (adjusted OR = 4.66, 95% CI: 1.06-20.51). BRAF and CIMP were also not statistically significantly associated with advanced colorectal neoplasia, even among those with SSP/As at the index colonoscopy.
Conclusion: There was no association between the molecular characteristics of serrated polyps and subsequent advanced colorectal neoplasia. However, among index SSP/As, we observed a strong association between MLH1 methylation and subsequent advanced neoplasia.
Citation Format: Xinwei Hua, Polly Newcomb, Jessica Chubak, Rachel Malen, Rebecca Ziebell, Aruna Kamineni, Lee-Ching Zhu, Melissa Upton, Hana Newman, Sheetal Hardikar, Andrea Burnett-Hartman. Association between molecular characteristics of serrated polyps and subsequent advanced colorectal neoplasia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3310.