P199 Clonal patterns between pouch neoplasia and prior colorectal neoplasia in Inflammatory Bowel Disease patients: an exploratory cohort study
Van Lierop, L.(1,2)*;te Groen, M.(2);Derikx, L.(2,3);Ylstra, B.(4);Hoentjen, F.(1,2);Nagtegaal, I.(5);Simmer, F.(5);
(1)University of Alberta Hospital, Gastroenterology, Edmonton, Canada;(2)Radboud University Medical Center, Gastroenterology, Nijmegen, The Netherlands;(3)Erasmus Medical Center, Gastroenterology, Rotterdam, The Netherlands;(4)Amsterdam UMC, Gastroenterology, Amsterdam, The Netherlands;(5)Radboud University Medical Center, Pathology, Nijmegen, The Netherlands;
Background
Inflammatory Bowel Disease (IBD) patients with an ileo-anal pouch anastomosis (IPAA) bear an increased risk of pouch neoplasia, with prior colorectal neoplasia as the strongest predictor. It is unknown if pouch neoplasia develops independently or is derived from prior colorectal neoplasia. Therefore, we aimed to elucidate the pathogenesis of pouch neoplasia by assessment of clonality between prior colorectal neoplasia and pouch neoplasia in IPAA patients with IBD.
Methods
In this explorative study we used the Dutch Nationwide Pathology Databank to identify IBD patients with both pouch neoplasia and prior colorectal neoplasia. Clonality was assessed on tissue with shallow whole genome sequencing based copy number aberration (CNA) analysis and validated with immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).
Results
Three out of 13 included patients showed clonally matching CNA profiles between colorectal neoplasia and pouch neoplasia, validated with matching IHC and FISH for p16 and HER2. Patients with clonal samples corresponded with concordant histology pre- and post IPAA, positive resection margins, metastasized disease or a short interval (<2 years) between colorectal and pouch neoplasia diagnoses.
Conclusion
CNA provides a feasible method for clonality assessment in patients with colorectal neoplasia and subsequent pouch neoplasia. Most pouch neoplasia in our cohort were molecularly different from their prior colorectal neoplasia. This may indicate a multifactorial pathogenesis of pouch neoplasia.