Biomarkers of Cancer Risk in Ulcerative Colitis (UC) Pouches Post Colectomy: A Pilot Study.
Wei Jiang, Ana E Bennett, Megan L Settle, Mary P Bronner. Cleveland Clinic, OH
Background: Patients with ulcerative colitis (UC) have an increased lifetime risk of colorectal neoplasia. This risk persists status post proctocolectomy with ileal pouch anal anastomosis (IPAA), but its impact on post colectomy pouch surveillance remains unclear. Currently, it is not possible to reliably distinguish the minority of UC pouch progressors who develop pouch neoplasia from nonprogressors who remain neoplasia free. Genomic biomarkers on native UC rectal biopsies have been reported to distinguish native UC progressors from nonprogressors. Similar better recognition of the pouch patients destined to develop neoplasia is also needed.
Design: Nondysplastic pouch biopsies from 10 randomly selected UC pouch nonprogressors were compared to nondysplastic distant pouch biopsies from 6 pouch progressors with carcinoma (n=4) or high grade dysplasia (n=2) located elsewhere in the pouch. Neoplastic pouch biopsies from two patients were selected as positive controls. Dual color fluorescence in situ hybridization (FISH) for cyclin D1 and its matched centromere (cyclin D1/CEP11) was performed. To enable analysis on paraffin-embedded, fixed archival tissue, methodology was developed using CAM5.2 immunohistochemistry with tyramide chromogen enhancement to isolate epithelial cells for FISH. A total of 50-100 epithelial cells were enumerated for FISH signals in each assay.
Results: Normal 2 arm + 2 centromere FISH signals in 10 UC pouch nonprogressor patients were present in 90% of cells/sample (range 86-96%) [figure 1]. Alternatively, nondysplastic biopsies from 6 pouch progressor patients revealed significantly greater FISH abnormalities, in that the normal FISH counts decreased to an average of 75% (range 68-83%) (p<0.001) [figure 1]. Positive control results using actual pouch adenocarcinoma tissues revealed even greater decreases in normal FISH counts to 32% and 36% of cells, respectively (p<0.001) [figure 1]. Of note, one of the six pouch progressors did not have native colonic neoplasia, reiterating that native colonic neoplasia status is not a reliable indicator of pouch progression.
Conclusions: This pilot study on UC pouch biopsies provides evidence that FISH alterations on archival paraffin block material holds promise as a cancer risk biomarker in the postcolectomy setting.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 63, Tuesday Afternoon