[656] Abnormal Cyclin D1 and Chromosome 11 Centromere Detected by FISH in Non-Dysplastic Surveillance Biopsies Predicts Pouch Neoplasia

Wei Jiang, Mary Bronner, Bonnie Shadrach, Xianrui Wu, Bo Shen, Xiuli Liu. Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA; University of Utah, Salt Lake City, UT; Cleveland Clinic, Cleveland, OH

Background: The occurrence of adenocarcinoma following restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) is an infrequent but lethal complication. Endoscopic biopsy surveillance has a low sensitivity for pouch neoplasia detection. The aim of this study was to determine if genomic biomarkers in non-dysplastic pouch/peripouch biopsies can improve neoplasia surveillance in patients with IPAA.
Design: Cyclin D1 (CCND1) and chromosome 11 centromere (CEP11) loci were analyzed by FISH in fixed, paraffin-embedded non-dysplastic pouch and peripouch biopsies from 13 patients with pouch neoplasia (progressors) and those without it (non-progressors, n=10). A total of 33 biopsies (16 from progressors and 17 from non-progressors) were examined. Results were expressed as % cells with abnormal CEP11 and/or CCND1 copy number.
Results: Loss of CCND1 and/or CEP11 was noted in more cells in non-dysplastic pouch biopsies from progressors than non-progressors (Table 1). In contrast, gain of cyclin D1 and/or CEP11 was noted more frequently in non-dysplastic biopsies from non-progressors than progressors. The distinction between progressor and non-progressor based on the loss of both CEP11 and CCND1 has an area under curve of 0.892 in ROC curve models (Figure 1).

Table 1. Frequency of CEP11 and CCND1 abnormality in non-dysplastic biopsies from UC patients with IPAA
Abnormality*ProgressorNonprogressorp value
CEP11 loss7.8 ± 6.13.4 ± 2.80.009
CCND1 loss11.7 ± 5.45.0 ± 3.60.00047
CEP11 or CCND1 loss14.0 ± 6.47.2 ± 4.90.0041
Loss of CEP11 and CCND15.5 ± 4.71.2 ± 1.40.00012
CEP11 gain3.7 ± 2.47.0 ± 4.00.012
CCND1 gain2.7 ± 2.25.2 ± 2.80.013
CEP11 or CCND1 gain5.1 ± 2.68.8 ± 3.60.004
Gain of CEP11 and CCND11.4 ± 1.43.5 ± 2.90.028
* Results were presented as % of cells, mean ± standard deviation

Conclusions: Genomic biomarkers in non-dysplastic pouch/peripouch biopsies distinguish progressors from non-progressors and improve neoplasia surveillance in patients with IPAA. Further studies are needed to confirm the current findings.
Category: Gastrointestinal

Tuesday, March 5, 2013 1:00 PM

Poster Session IV # 126, Tuesday Afternoon


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