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).
|CEP11 loss||7.8 ± 6.1||3.4 ± 2.8||0.009|
|CCND1 loss||11.7 ± 5.4||5.0 ± 3.6||0.00047|
|CEP11 or CCND1 loss||14.0 ± 6.4||7.2 ± 4.9||0.0041|
|Loss of CEP11 and CCND1||5.5 ± 4.7||1.2 ± 1.4||0.00012|
|CEP11 gain||3.7 ± 2.4||7.0 ± 4.0||0.012|
|CCND1 gain||2.7 ± 2.2||5.2 ± 2.8||0.013|
|CEP11 or CCND1 gain||5.1 ± 2.6||8.8 ± 3.6||0.004|
|Gain of CEP11 and CCND1||1.4 ± 1.4||3.5 ± 2.9||0.028|