Utility of DNA Flow Cytometric Analysis of Paraffin-embedded Tissue in the Risk Stratification and Management of 'Indefinite for dysplasia' in Patients With Inflammatory Bowel Disease.

Abstract

The clinical significance of 'indefinite for dysplasia' [IND] in patients with inflammatory bowel disease remains unclear. Currently, no biomarker can reliably differentiate reactive changes from true dysplasia and/or risk stratify IND. A total of 52 IND colon biopsies were analysed by DNA flow cytometry. The follow-up result of each biopsy was determined by reviewing all subsequent biopsies and endoscopic reports for the occurrence of high-grade dysplasia [HGD] or colorectal cancer [CRC] at the site of previous biopsy or in the same segment of colon. The overall 1-, 3-, 5-, and 7-year detection rates of HGD or CRC in all 52 IND cases were 4.6% (95% confidence interval [CI], 0.0%-10.6%), 18.2% [95% CI, 3.5%-30.7%], 26.3% [95% CI, 8.4%-40.7%], and 31.6% [95% CI, 11.2%-47.4%], respectively. More interestingly, 10.6% of IND cases with aneuploidy were subsequently found to have HGD or CRC within 1 year [95% CI, 0.0%-23.7%], with 36.4% [95% CI, 7.1%-56.5%], 51.7% [95% CI, 16.1%-72.2%], and 59.8% [95% CI, 21.4%-79.5%] detected within 3, 5, and 7 years, respectively. By comparison, in the setting of normal DNA content, 1-, 3-, 5-, and 7-year detection rates of HGD or CRC were 0.8% [95% CI, 0.0%-2.7%], 3.3% [95% CI, 0.0%-9.6%], 5.2% [95% CI, 0.0%-14.7%], and 6.5% [95% CI, 0.0%-18.1%], respectively. Only the presence of aneuploidy was found to be a significant predictor of HGD or CRC with the estimated univariate and multivariate hazard ratios of 13.8 [p = 0.016] and 50.3 [p = 0.010], respectively. IND may not be a low-risk condition for HGD or CRC. In this regard, the presence of aneuploidy can identify a subset of IND cases that are at increased risk for subsequent detection of HGD or CRC.