Abstract IA35: Molecular characterization of sessile serrated adenoma/polyps: A risk factor for higher colorectal cancer that further associates with endometrial polyps in female African Americans

Abstract

Abstract Colorectal cancer is the third leading cause of cancer-related deaths in the United States, and rates are highest among African Americans (AAs). Sessile serrated adenoma/polyps (SSA/Ps) may be precursors to up to 30% of all colorectal cancers. Flat and mucinous features make SSA/Ps difficult to detect and diagnose. As such, there is a need for specific sensitive molecular biomarkers for an accurate and reliable diagnosis. Our aim was to assess the diagnostic value of molecular biomarkers that may distinguish SSA/Ps from benign hyperplastic polyps (HPs) among AA SSA/P patients. We conducted a retrospective study of all colonoscopies (n=12,085) performed at Howard University Hospital (2010-2015), which confirmed 4,070 AA patients with polyps, including 252 with SSA/Ps. Gene expression and mutation frequency profiles were analyzed in a total of 47 patients (62 specimens: 29 SSA/Ps, 26 HPs, 3 tubular adenomas, and 4 normal tissues). We tested 4 transcripts (MUC6, FSCN1, SEMG1, and TRNP1) using qRT-PCR. MSI and BRAF mutations were analyzed. CIMP analysis was performed using CACNA1G, IGF2, NEUROG1, RUNX, SOCS, and MLH1. In a parallel study, we assessed the association between endometrial polyp occurrence in patients with different types of colorectal lesions. MUC6, SEMG1, TRNP1, and FSCN1 were significantly more expressed in SSA/Ps vs. HPs (P<0.05; fold differences of 37.2, 10.7, 5.8 and 2.5, respectively). BRAF mutation was found in 55.6% of SSA/Ps vs. 12.0% in HPs (P = 0.001). The frequency of CIMP was higher in SSA/Ps but not statistically significant, while MSI was more prevalent in HPs (P > 0.05). There was a higher loss of MLH1 expression in HPs than SSA/Ps (42.9% showing expression vs 70.3% IHC staining >=2 in HPs and SSA/Ps). The SSA/Ps in our AA study were primarily distal (67%). In female patients, SSA/Ps associated with the higher frequency of endometrial polyps (8% vs. 2% in controls, p=0.003). Our results show that MUC6-SEMG1-TRNP1 expression and BRAF mutation have the strongest correlation with SSA/Ps. The distal location might help explain why MSI and CIMP may not be optimal molecular biomarkers in African American patients with SSA/Ps. These markers may be of high relevance for the diagnosis of ambiguous lesions and will benefit patients’ management for scheduling follow-ups based on the nature of index lesions. Females with colon lesions of the SSA/Ps type might benefit from a screening for an endometrial polyp in an age-independent manner. Citation Format: Hassan Ashktorab, Saman Azam, Babak Shokrani, Edward Lee, Taraneh Arjomand, Priyanka Kanth, Don Delker, Adeyinka Laiyemo, John Caretheres, Mehdi Nouraie, Hassan Brim. Molecular characterization of sessile serrated adenoma/polyps: A risk factor for higher colorectal cancer that further associates with endometrial polyps in female African Americans [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr IA35.