Abstract 3159: Do molecular markers differentiate between sessile serrated adenoma/polyps and hyperplastic polyps
Authors: Ashktorab Hassan , Azam Saman , Tarjoman Taraneh , Kanth Priyanka , Lee Edward , Nouraie Mehdi , Atefi Nazli , Shokrani Babak , Laiyemo Adeyinka , Goel Ajay , Hazel Mark W. , Yao Ruoxin , Snow Angela , Neklason Deborah , Delker Don , Brim Hassan 
Published: August 2019

Background: A significant proportion of colorectal cancers, as much as up to 30%, develop through the alternate serrated pathway. The precursor lesions in this pathway comprise of sessile serrated adenomas or polyps (SSA/SSPs) and hyperplastic polyps (HPs), both with a varying risk-profile associated with them for progression into colorectal cancer. Although both types of polyps can be identified histologically, the clinical challenge for gastroenterologists and pathologists remain for risk-prediction as to which of these polyps have a higher likelihood for subsequent development and progression into colorectal cancer. These data highlight the imperative need for the development of more specific and objective markers that can adequately differentiate between the two types of colonic polyps.

Aim: The aim of our study was to determine a variety of molecular biomarkers that may distinguish SSA/Ps and HPs, and to establish biomarker profiles that associate with low vs. high-risk SSA/Ps.

Methods: We conducted a retrospective study of all colonoscopies (n=12,085) performed at the Howard University Hospital between January 2010 to December 2015; of which 83% were conducted in patients of African American (AA) descent (n=10,027). Among AAs, pathology reports confirmed 4,070 patients with polyps, including 252 with SSA/Ps. Gene expression and mutation frequency profiles were analyzed in a total of 47 patients which included 62 specimens (29 SSPs, 26 HP, 3 tubular adenomas (TA) and 4 normal colonic tissues). From a panel of 51 candidate transcripts, we validated 4 RNA markers (MUC6, FSCN1, SEMG1, and TRNP1) using qRT-PCR. MSI and BRAF mutations were also analyzed. CIMP analysis was performed for the aberrant methylation of CACNA1G, IGF2, NEUROG1, RUNX, SOCS and MLH1. The frequency of gender, age groups, anatomic location, clinical/pathological symptoms and reason for colonoscopy in SSA/P patients was analyzed. The median age range for SSA/P diagnosis was between 50 to 64 years.

Results: MUC6, SEMG1, TRNP1, and FSCN1 expression was significantly higher in SSA/Ps vs. HPs (P &lt; 0.05); with corresponding fold differences of 37.2 10.7, 5.8 and 2.5, respectively. BRAF mutations were found in 55.6% of SSA/Ps as opposed to 12.0% of HPs (P &lt; 0.05). The frequency of CIMP was higher in SSA/Ps and correlated with BRAF mutation, while the degree of MSI was more prevalent in HP (P &gt; 0.05). SSA/P lesions were distal (67%).

Conclusion: Our results show that MUC6 and SEMG1 expression and BRAF mutation have the strongest correlation with SSA/Ps in comparison to HPs. In addition, SSA/Ps were predominantly distal in location. These are novel and distinguishing features compared to the published literature in non-AA populations and may help explain why MSI and CIMP, usually linked to proximal lesions, are not optimal molecular biomarkers in AA patients with such serrated lesions.

Note: This abstract was not presented at the meeting.

Citation Format: Hassan Ashktorab, Saman Azam, Taraneh Tarjoman, Priyanka Kanth, Edward Lee, Mehdi Nouraie, Nazli Atefi, Babak Shokrani, Adeyinka Laiyemo, Ajay Goel, Mark W. Hazel, Ruoxin Yao, Angela Snow, Deborah Neklason, Don Delker, Hassan Brim. Do molecular markers differentiate between sessile serrated adenoma/polyps and hyperplastic polyps [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 3159.