Association of Aneuploidy and Flat Dysplasia With Development of High-Grade Dysplasia or Colorectal Cancer in Patients With Inflammatory Bowel Disease

Tsai, Jia-Huei; Rabinovitch, Peter S.; Huang, Danning; Small, Thomas; Mattis, Aras N.; Kakar, Sanjay; Choi, Won‐Tak

doi:10.1053/j.gastro.2017.08.031

Cited by 51 publications

(79 citation statements)

References 20 publications

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“…Multiple aneuploid peaks were present in three biopsies (21%) (Figure C). We have previously demonstrated that it is extremely rare to find aneuploidy in non‐dysplastic IBD biopsies (0–4%) . Consistent with our previous finding, FCM performed on three non‐dysplastic biopsies from three CCA patients showed normal DNA content (Figure ).…”

Section: Resultssupporting

confidence: 88%

“…If a pathologist cannot make a diagnosis of dysplasia even in the presence of FCM abnormalities, it is important to mention the FCM results in the report (if available) and acknowledge some risk of subsequent development of HGD or CRC in these patients . In support of this, using paraffin‐embedded tissue, we recently reported a high rate of aneuploidy in flat LGD (40.5%) and flat HGD (93.3%), and there was a significant correlation between aneuploidy and a subset of flat LGD with increased risk for subsequent detection of HGD or CRC with the estimated univariate and multivariate HRs of 5.3 ( P = 0.006) and 4.5 ( P = 0.040), respectively . In fact, more than 50% of flat LGD patients with aneuploidy were diagnosed with HGD or CRC within 1 year, whereas only 4.6% of flat LGD patients with normal DNA content developed HGD or CRC ( P < 0.001).…”

Section: Discussionmentioning

confidence: 80%

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DNA flow cytometric and interobserver study of crypt cell atypia in inflammatory bowel disease

Wen

Umetsu

Goldblum³

et al. 2019

Histopathology

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Aims The pathological features and diagnostic reliability of crypt cell atypia (CCA) arising in inflammatory bowel disease (IBD) and its clinical significance are unknown. Methods and results DNA flow cytometry (FCM) was performed on 14 colon biopsies of CCA from seven IBD patients (male‐to‐female ratio, 5:2; mean age, 53 years; mean IBD duration, 15 years) using paraffin‐embedded tissue. Seven gastrointestinal pathologists were asked to diagnose each biopsy as negative for dysplasia (NEG), indefinite for dysplasia (IND), low‐grade dysplasia (LGD) or high‐grade dysplasia (HGD) by morphology alone, then again with knowledge of FCM results. Aneuploidy was detected in all 14 biopsies, and five of eight biopsies (63%) also showed strong and diffuse nuclear staining for p53 in the areas of CCA. Six (86%) patients developed HGD (n = 5) or adenocarcinoma (n = 1) in the same colonic segment where CCA had been diagnosed within a mean follow‐up time of 27 months. No follow‐up information was available in the remaining one patient. When diagnoses were grouped as NEG or ‘atypical’ (including IND, LGD or HGD), the overall agreement rate of 76% (kappa = 0.51) based on morphology alone improved to 90% (kappa = 0.81) with knowledge of FCM results. Even when categorised as NEG or dysplasia (LGD or HGD) with each of the IND diagnoses reclassified into three categories (NEG, LGD or HGD) based on the degree of suspicion for dysplasia, the overall agreement rate of 63% (kappa = 0.25) based on morphology alone improved to 73% (kappa = 0.46) with knowledge of FCM results. However, when grouped as NEG, LGD or HGD, the overall agreement rate was less than 40% (kappa < 0.09) regardless of knowledge of FCM results. Conclusions The presence of aneuploidy, p53 positivity and development of HGD or adenocarcinoma on follow‐up indicate that CCA likely represents a dysplastic lesion (at least LGD) and is a histological marker of neoplastic progression. Although the grading of CCA, largely based on cytological abnormalities, is subject to significant interobserver variability, CCA can be histologically identified and should lead to a recommendation of increased endoscopic surveillance, especially if aneuploidy is detected.

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Section: Resultssupporting

confidence: 88%

Section: Discussionmentioning

confidence: 80%

DNA flow cytometric and interobserver study of crypt cell atypia in inflammatory bowel disease

Wen

Umetsu

Goldblum³

et al. 2019

Histopathology

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“…Fusobacterium nucleatum numbers are significantly correlated with tumor size, and shortened survival times in a population of human Japanese patients with later stage CRC compared to earlier stages 53. These findings, as well as additional observations in rodent models and humans with CRC suggest that chronic inflammatory disease of the GI tract is a potential risk factor for the development of additional channels for amplified inflammatory processes, aneuploidy, high‐grade dysplasia, metaplasia and loss of cellular proliferative checkpoints, all of which are processes that can be appreciated in malignancy 13, 19, 54, 58, 59. The increased numbers of mucosal Fusobacterium spp.…”

Section: Discussionmentioning

confidence: 80%

“…Although incompletely understood, GI inflammation‐mediated progression to cancer development might involve bacterial toxin production, release of alarmins, gut biofilm modification, dysregulation of gut barrier function, suppression of anti‐inflammatory mediators and transition through an element of high grade dysplasia to cell damage and aneuploidy 13, 19, 35, 40, 60, 61, 62…”

Section: Discussionmentioning

confidence: 99%

“…Various risk factors including genetic and molecular alterations,3, 4, 5 diet,3, 6, 7 and chronic inflammation8, 9, 10 have been linked to the development of both disorders. Still other studies have suggested an association between chronic mucosal inflammation and the progression of IBD to pronounced dysplasia in the GI tract 11, 12, 13, 14…”

Section: Introductionmentioning

confidence: 97%

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Relationship of the mucosal microbiota to gastrointestinal inflammation and small cell intestinal lymphoma in cats

Garraway

Johannes

Bryan

et al. 2018

Veterinary Internal Medicne

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BackgroundThe gastrointestinal (GI) microbiota in healthy cats is altered in IBD. Little research has been performed to identify whether specific bacterial groups are associated with small cell GI lymphoma (LSA).HypothesisMucosal bacteria, including Enterobacteriaceae and Fusobacterium spp., are abundant in intestinal biopsies of cats with small cell GI LSA compared to cats with IBD.AnimalsFourteen cats with IBD and 14 cats with small cell GI LSA.MethodsRetrospective case control study. A search of the medical records was performed to identify cats diagnosed with IBD and with GI LSA. Bacterial groups identified by FISH in GI biopsies were compared between cohorts and correlated to CD11b+ and NF‐κB expression.Results Fusobacterium spp. (median; IQR bacteria/region) were higher in cats with small cell GI LSA in ileal (527; 455.5 – 661.5; P = .046) and colonic (404.5; 328.8 – 455.5; P = .016) adherent mucus, and combined colonic compartments (free mucus, adherent mucus, attaching to epithelium) (8; 0 – 336; P = .017) compared to cats with IBD (ileum: 67; 31.5 – 259; colon: 142.5; 82.3 – 434.5; combined: 3; 0 – 34). Bacteroides spp. were higher in ileal adherent mucus (P = .036) and 3 combined ileal compartments (P = .034) of cats with small cell GI LSA. There were significant correlations between Fusobacterium spp. totals and CD11b+ cell (P = .009; rs .476) and NF‐κB expression (P = .004; rs .523).ConclusionsThe bacterial alterations appreciated might be influential in development of small cell GI LSA, and should drive further studies to elucidate the effects of microbial‐mediated inflammation on GI cancer progression.

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UC Surveillance

Choi¹,

Bakir²

2019

Biomarkers in Inflammatory Bowel Diseases

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Association of Aneuploidy and Flat Dysplasia With Development of High-Grade Dysplasia or Colorectal Cancer in Patients With Inflammatory Bowel Disease

Cited by 51 publications

References 20 publications

DNA flow cytometric and interobserver study of crypt cell atypia in inflammatory bowel disease

DNA flow cytometric and interobserver study of crypt cell atypia in inflammatory bowel disease

Relationship of the mucosal microbiota to gastrointestinal inflammation and small cell intestinal lymphoma in cats

UC Surveillance

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