DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis

doi:10.1016/0016-5085(92)91185-7

Gastroenterology

Volume 103, Issue 5, November 1992, Pages 1611-1620

https://doi.org/10.1016/0016-5085(92)91185-7 Get rights and content

Abstract

The objective of the present study was to determine whether abnormal epithelial DNA content (aneuploidy) in colonic biopsy specimens from ulcerative colitis (UC) patients correlated with and predicted histological progression to dysplasia. Aneuploidy was absent in 20 low-cancer risk patients. In 81 high-cancer risk patients aneuploidy correlated significantly with the severity of histological abnormality (negative, indefinite, dysplasia, or cancer). Statistically our data suggest that many more biopsy specimens than are usually taken are needed to detect focal dysplastic lesions. Prospective study of 25 high risk patients without dysplasia revealed 5 with aneuploidy, all of whom progressed to dysplasia in 1–2.5 years, whereas 19 patients without aneuploidy did not progress to either aneuploidy or dysplasia within 2–9 years. Our data indicate that aneuploidy in mucosal biopsy specimens correlates with histological grade and identifies a subset of patients without dysplasia who are more likely to develop it. It was concluded that more frequent and extensive colonoscopic surveillance of this minority subset of high risk patients and less frequent surveillance in the remaining majority may reduce cost and detect more curable lesions.

References (30)

DS Levine et al.
Endoscopic biopsy technique for acquiring larger mucosal samples
Gastrointest Endosc
(1991)
RH Riddell et al.
Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical implications
Hum Pathol
(1983)
BJ Reid et al.
Barrett's esophagus: flow cytometry complements histology in detection of patients at risk for adenocarcinoma
Gastroenterology
(1987)
DS Levine et al.
Distribution of aneuploid cell populations in ulcerative colitis with dysplasia or cancer
Gastroenterology
(1991)
BJ Reid et al.
Progression to malignancy in Barrett's esophagus: endoscopic, histologic and flow cytometric follow-up of a cohort
Gastroenterology
(1992)
GC Burmer et al.
Neoplastic progression in ulcerative colitis: histology, DNA content and loss of a p53 allele
Gastroenterology
(1992)
R Löfberg et al.
Colonoscopic surveillance in long-standing total ulcerative colitis—a 15-year follow-up study
Gastroenterology
(1990)
DM Melville et al.
Dysplasia and deoxyribonucleic acid aneuploidy in the assessment of precancerous changes in chronic ulcerative colitis
Gastroenterology
(1988)
B Barlogie et al.
Prognostic implications of ploidy and proliferative activity in human solid tumors
Cancer Genet Cytogenet
(1982)
FW Nugent et al.
Cancer surveillance in ulcerative colitis: results of a 13-year prospective biopsy surveillance program
Gastroenterology
(1991)

P Prior et al.

Cancer morbidity in ulcerative colitis

Gut

(1982)

A Ekbom et al.

Ulcerative colitis and colorectal cancer. A population-based study

N Engl J Med

(1990)

JH Collins et al.

Colon cancer, dysplasia and surveillance in patients with ulcerative colitis

N Engl J Med

(1987)

JE Lennard-Jones

Compliance, cost and common sense limit cancer control in colitis

Gut

(1986)

KA Alanen et al.

Autolysis is a potential source of false aneuploid peaks in flow cytometric DNA histograms

Cytometry

(1989)

Cited by (518)

Poor Diagnostic Reproducibility in the Identification of Nonconventional Dysplasia in Colitis Impacts the Application of Histologic Stratification Tools
2024, Modern Pathology
Due to their increased cancer risk, patients with longstanding inflammatory bowel disease are offered endoscopic surveillance with concomitant histopathologic assessments, aimed at identifying dysplasia as a precursor lesion of colitis-associated colorectal cancer. However, this strategy is beset with difficulties and limitations. Recently, a novel classification criterion for colitis-associated low-grade dysplasia has been proposed, and an association between nonconventional dysplasia and progression was reported, suggesting the possibility of histology-based stratification of patients with colitis-associated lesions. Here, a cohort of colitis-associated lesions was assessed by a panel of 6 experienced pathologists to test the applicability of the published classification criteria and try and validate the association between nonconventional dysplasia and progression. While confirming the presence of different morphologic patterns of colitis-associated dysplasia, the study demonstrated difficulties concerning diagnostic reproducibility between pathologists and was unable to validate the association of nonconventional dysplasia with cancer progression. Our study highlights the overall difficulty of using histologic assessment of precursor lesions for cancer risk prediction in inflammatory bowel disease patients and suggests the need for a different diagnostic strategy that can objectively identify high-risk phenotypes.
DNA flow cytometry for detection of genomic instability as a cancer precursor in the gastrointestinal tract
2024, Methods in Cell Biology
One of the earliest applications of flow cytometry was the measurement of DNA content in cells. This method is based on the ability to stain DNA in a stoichiometric manner (i.e., the amount of stain is directly proportional to the amount of DNA within the cell). For more than 40 years, a number of studies have consistently demonstrated the utility of DNA flow cytometry as a potential diagnostic and/or prognostic tool in patients with most epithelial tumors, including pre-invasive lesions (such as dysplasia) in the gastrointestinal tract. However, its availability as a clinical test has been limited to few medical centers due to the requirement for fresh tissue in earlier studies and perceived technical demands. However, more recent studies have successfully utilized formalin-fixed paraffin-embedded (FFPE) tissue to generate high-quality DNA content histograms, demonstrating the feasibility of this methodology. This review summarizes step-by-step methods on how to perform DNA flow cytometry using FFPE tissue and analyze DNA content histograms based on the published consensus guidelines in order to assist in the diagnosis and/or risk stratification of many different epithelial tumors, with particular emphasis on dysplasia associated with Barrett's esophagus and inflammatory bowel disease.
Conventional and non-conventional dysplasia in patients with inflammatory bowel disease
2023, Annales de Pathologie
Par rapport à la population générale, les patients atteints d’une maladie inflammatoire chronique de l’intestin (MICI), qu’il s’agisse d’une rectocolite hémorragique (RCH) ou d’une maladie de Crohn (MC), présentent un risque accru de développer certains cancers, en particulier les cancers colorectaux (CCR). Les CCR, dont la grande majorité sont des adénocarcinomes, se développent à partir d’une lésion précancéreuse appelée dysplasie (ou néoplasie intra-épithéliale), selon une séquence inflammation–dysplasie–adénocarcinome. L’avènement de nouvelles techniques d’endoscopie, notamment de techniques de visualisation et de résection, a conduit à revoir la classification des lésions de dysplasie, qui sont désormais classées en lésions visibles ou invisibles, ainsi que leur prise en charge thérapeutique, avec une approche plus conservatrice du cadre colorectal. Par ailleurs, à côté de la dysplasie conventionnelle, de phénotype intestinal, classiquement décrite dans les MICI, sont désormais décrites des dysplasies non conventionnelles (par opposition à la dysplasie conventionnelle de phénotype intestinal), qui sont au nombre de sept. La reconnaissance de ces sous-types non conventionnels encore mal connus des pathologistes devient cruciale, car certains de ces sous-types semblent être à risque élevé de développer une néoplasie avancée (c.-à-d. une dysplasie de haut grade ou un CCR). Cette revue décrit brièvement les caractéristiques macroscopiques des lésions dysplasiques dans les MICI, ainsi que leur prise en charge thérapeutique, puis les caractéristiques clinicopathologiques de ces lésions dysplasiques, en insistant plus particulièrement sur les nouveaux sous-types de dysplasie non conventionnelle, à la fois d’un point de vue morphologique et moléculaire.
Compared to the general population, patients with inflammatory bowel disease (IBD), both ulcerative colitis (UC) or Crohn's disease (CD), are at increased risk of developing some cancers, particularly colorectal cancers (CRC). CRCs, the vast majority of which are adenocarcinomas, develop from a precancerous lesion called dysplasia (or intraepithelial neoplasia) via an inflammation–dysplasia–adenocarcinoma sequence. The advancements of new endoscopic techniques, including visualisation and resection techniques, has led to a reclassification of dysplasia lesions into visible and invisible lesions and their therapeutic management, with a more conservative approach to the colorectal setting. In addition, besides conventional dysplasia, of intestinal phenotype, classically described in IBD, non-conventional dysplasias (as opposed to conventional dysplasia of intestinal phenotype) are now described, including at least seven subtypes. Recognition of these unconventional subtypes, which are still poorly known from pathologists, is becoming crucial, as some of these subtypes appear to be at high risk of developing advanced neoplasia (i.e. high-grade dysplasia or CRC). This review briefly describes the macroscopic features of dysplastic lesions in IBD, as well as their therapeutic management, followed by the clinicopathological features of these dysplastic lesions, with particular emphasis on the new subtypes of unconventional dysplasia, both from a morphological and molecular point of view.
Molecular characterization of visible low-grade dysplastic lesions in patients with inflammatory bowel disease
2023, Human Pathology
We studied pathogenic gene mutations and tumor mutation burden (TMB) in visible low-grade dysplastic lesions in patients with inflammatory bowel disease (IBD). The dysplastic lesions with histologically normal mucosa in the background (group 1) were compared with dysplastic lesions occurring either in a background of chronic active colitis (group 2) or associated with synchronous carcinomas regardless of the status of the background mucosa (group 3). The TMB in group 3 was consistently higher in comparison to the group 1 and group 2 lesions, although the difference was not statistically significant. There also seem to be different mutation profiles between the groups, indicating different pathways of tumor pathogenesis. More frequent APC mutations were seen in group 1 as compared to other groups and TP53 mutations were seen in groups 2 and 3, but none in group 1. Molecular characterization could potentially be used as an ancillary prognostic marker in challenging cases to guide the further management of IBD patients with visible dysplastic lesions.
Colorectal Cancer in Inflammatory Bowel Disease: Mechanisms and Management
2022, Gastroenterology
Patients with inflammatory bowel disease (IBD) are at increased risk of developing colorectal cancer (CRC), despite decreases in CRC incidence in recent years. Chronic inflammation is the driver of neoplastic progression, resulting in dysplastic precursor lesions that may arise in multiple areas of the colon through a process of field cancerization. Colitis-associated CRC shares many molecular similarities with sporadic CRC, and preclinical investigations have demonstrated a potential role for the microbiome in concert with the host immune system in the development of colitis-associated colorectal cancer (CAC). Some unique molecular differences occur in CAC, but their role in the pathogenesis and behavior of inflammation-associated cancers remains to be elucidated. Nonconventional types of dysplasia have been increasingly recognized, but their natural history is not well defined, and they have not been incorporated into surveillance algorithms. The concept of cumulative inflammatory burden highlights the importance of considering histologic inflammation over time as an important risk factor for CAC. Dysplasia is arguably the most important risk factor for developing CAC, and advances have been made in the endoscopic detection and removal of precancerous lesions, thereby deferring or avoiding surgical resection. Some of the agents used to treat IBD are chemopreventive. It is hoped that by gaining better control of the underlying inflammation with newer medications and better endoscopic detection and management, a more sophisticated appreciation of clinicopathologic risk factors, and growing awareness of the genetic, immunologic, and environmental causes of colitis- associated neoplasia, that colitis-associated colorectal neoplasia will become even more predictable and manageable in the coming years.
AGA Clinical Practice Update on Endoscopic Surveillance and Management of Colorectal Dysplasia in Inflammatory Bowel Diseases: Expert Review
2021, Gastroenterology
Improvements in disease management, as well as endoscopic technology and quality, have dramatically changed the way in which we conceptualize and manage inflammatory bowel disease–related dysplasia over the past 20 years. Based on evolving literature, we propose a conceptual model and best practice advice statements for the prevention, detection, and management of colorectal dysplasia in people with inflammatory bowel disease. This expert review was commissioned and approved by the American Gastroenterological Association Institute Clinical Practice Updates Committee and the American Gastroenterological Association Governing Board to provide timely guidance on a topic of high clinical importance to the American Gastroenterological Association membership. It underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology.

View all citing articles on Scopus

: Supported by National Institutes of Health grant PO1 DK32971.

View full text

DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis

Abstract

Gastrointest Endosc

Hum Pathol

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Cancer Genet Cytogenet

Gastroenterology

Cancer morbidity in ulcerative colitis

Gut

Ulcerative colitis and colorectal cancer. A population-based study

N Engl J Med

Colon cancer, dysplasia and surveillance in patients with ulcerative colitis

N Engl J Med

Compliance, cost and common sense limit cancer control in colitis

Gut

Autolysis is a potential source of false aneuploid peaks in flow cytometric DNA histograms

Cytometry