Fecal methylated markers for the detection of adenocarcinoma in Ileal pouches of patients with underlying ulcerative colitis

Abstract

Listen

Translate article

Patients with ulcerative colitis and Crohn's disease undergo total abdominal colectomy and ileal pouch anal anastomosis (IPAA) as choice procedures to alleviate symptoms associated with their disease. Although the surgical procedure substantially reduces the risk for colon cancer and dysplasia in patients with ulcerative colitis, there is occurrence of adenocarcinoma in patients with IPAA. The risk and incidence for pouch cancer has increasingly been recognized in recent years. Based on our clinical experience, surveillance pouch endoscopy with routine H & E histology has missed adenocarcinoma of the pouch. Better markers are needed for early and accurate detection of dysplasia. Our aim was to assess methylated genetic markers for the detection of dysplasia and adenocarcinoma using fecal samples from ulcerative colitis patients with IPAA. Ulcerative colitis patients with IPAA diagnosed with adenocarcinoma of the pouch were recruited from our subspecialty Pouchitis Clinic. Patients who underwent sequential surveillance pouch endoscopy were included. Diagnosis of pouch adenocarcinoma was confirmed by re-review of biopsy and resection specimens by a GI pathologist. DNA materials were extracted from archived fecal samples from the diagnostic or surveillance pouch endoscopy, and blindly analyzed 6 methylated DNA markers BMP3, ALX4, EY2, EY4, UNC5, and GA5 which have been known to be involved in colorectal cancer (CRC) progression and tumorigenesis. Three patients were studied. Demographics, timeline of disease progression and presence of methylated genes are elucidated in the Table. One patient died 4 months after cancer was diagnosed and one patient died 17 months after cancer was diagnosed No Caption available. No Caption available. In our study we demonstrated that six genes commonly methylated in CRC are also methylated in patients with pouch adenocarcinoma; that methylation of the genes occur before histological evidence of dysplasia/adenocarcinoma in pouchitis patients; and that fecal DNA assay may provide an adjunct tool for early and accurate detection of pouch neoplasm.