The AGA Journals Blog highlights the latest discoveries in gastroenterology and hepatology research.

Which Patients With Flat Low-grade Dysplasia are at High Risk for Colorectal Cancer?

Detection of flat low-grade dysplasia (fLGD) and aneuploidy in colon tissues increases risk for high-grade dysplaisa (HGD) or colorectal cancer (CRC) more than 5-fold in patients with inflammatory bowel disease (IBD), researchers report in the December issue of Gastroenterology. Aneuploidy was also detected in almost all cases of flat HGD (fHGD)

(A) Flat LGD (H&E, 100×). (B) Flow cytometry histogram shows a discrete peak of aneuploid cells (red) that can be distinguished from normal diploid cells (green) from a patient with fLGD.

IBD is a risk factor for CRC. Colonoscopic surveillance aims to reduce CRC incidence by detecting pre-invasive, dysplastic lesions. Patients with colitis have a low risk of colorectal cancer after resection of polypoid dysplasia, but some dysplastic lesions are flat, making them more difficult to detect and/or resect endoscopically.

Colectomy is recommended for patients with fHGD because of its association with CRC, but it is not clear what to do about patients with IBD and fLGD—some of these patients develop HGD or CRC, but reported rates of progression range from none to >50%.

Studies that examined a potential correlation between aneuploidy and IBD-related dysplasia did not analyze DNA content in flat dysplasia or correlate histologic grade of dysplasia with patient outcome.

Jia-Huei Tsai et al performed a retrospective analysis of formalin-fixed paraffin-embedded colon tissues with fLGD from 37 patients undergoing surveillance colonoscopy for IBD.

Using flow cytometry analysis of paraffin-embedded colon tissue, they detected aneuploidy in 15 of 37 samples with fLGD (40.5%). Over mean follow-up time of 37 months, 9/15  patients with fLGD and aneuploidy were subsequently found to have HGD or CRC (60%) , whereas only 3  of the remaining 22 patients with fLGD (without signs of aneuploidy) developed HGD or CRC (13.6%).

HGD or CRC developed in all patients with fLGD and aneuploidy followed for 12 years. However, in patients with fLGD and no aneuploidy, HGD or CRC developed in only 22.3% of patients followed for 12 years.

Tsai et al calculated a univariate hazard ratio for subsequent detection of HGD or colorectal cancer in patients with fLGD and aneuploidy of 5.3 (95% CI, 1.542−24.121) over a mean follow-up time of 37 months. No other factors were found to be significantly associated with an increased risk for HGD or CRC in these patients.

In contrast, Tsai et al detected aneuploidy in 14 of 15 samples with fHGD (93.3%) and 2 of 45 samples that were negative for dysplasia (4.4%). Four of the 10 patients with fHGD and aneuploidy (40%) had concurrent or subsequent CRC, within a mean follow-up time of 2.7 months.

The authors conclude that up to 42.7% of patients with fLGD are found to have HGD or CRC within the following 5 years. An earlier study reported that up to 53% of patients with fLGD developed HGD or CRC within 5 years, but there were no other factors for distinguishing patients who did vs did not devleop neoplasia. Tsai et al show that patients with fLGD and aneuploidy have a more than 5-fold increase in risk for HGD or CRC.

These patients could benefit from early colectomy or increased colonoscopic surveillance.

However, the flow cytometric assessment of aneuploidy as a marker of HGD or CRC in patients with fLGD requires validation in a larger, prospective study.



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Kristine Novak

Kristine Novak

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About The Author:

Dr. Kristine Novak

Dr. Kristine Novak

Dr. Kristine Novak is a science writer and editor based in San Francisco. She has extensive experience covering gastroenterology, hepatology, immunology, oncology, clinical, and biotechnology research discoveries.

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