The role of adenoma for colorectal cancer development: Differences in the distribution of adenoma with low-grade dysplasia, high-grade dysplasia, and cancer that invades the submucosa

Background & Aims: Colorectal cancer represents the third most common malignancy and the fourth most common cause of cancer death worldwide. The existence of drug-resistant colon cancer stem cells is thought to be one of the most important reasons behind treatment failure in colon cancer, their existence putatively leading to metastasis and recurrences. The aim of our study was to investigate the immunoexpression patterns of CD133 and CD166 in colon carcinoma, both individually and in combination, assessing their significance as prognostic markers.Methods. A total of 45 retrospective colon adenocarcinoma cases were investigated by enzymatic and multiple fluorescence immunohistochemistry for their CD133 and CD166 expression and colocalization.Results. Both CD133 and CD166 were expressed to different extents in all cancer specimens, with apredominant cytoplasmic pattern for CD133 and a more obvious membranous-like pattern for CD166.Overall, when comparing their reactivity for the tumoral tissue, CD166 expression areas seemed to be smaller than those of CD133. However, there was a direct correlation between CD133 and CD166 expression levels throughout the entire spectrum of lesions, with higher values for dysplastic lesions. Colocalization of CD133/ CD166 was obvious at the level of cells membranes, with higher coeficients in high grade dysplasia, followed by well and moderate differentiated tumours.Conclusions. CD133/CD166 colocalization is an early event occurring in colon tumorigenesis, with thehighest coeficients recorded for patients with high grade dysplasia, followed by well differentiated tumours. Thus, we consider that the coexpression of these two markers could be useful for further prognostic andtherapeutically stratification of patients with colon cancer.Abbreviations: AJCC - American Joint Committee on Cancer; CCD - charge-coupled device camera sensor; CD133 - prominin-1 (PROM1); CD166 - Activated Leukocyte Cell Adhesion Molecule (ALCAM); CRC - colorectal cancer; CSC - cancer stem cells; DAB - 3,3'-diaminobenzidine chromogen; DAPI - 4',6-diamidino- 2-phenylindole; HE - Hematoxylin and eosin staining; HGD - high grade dysplasia; HRP - horseradish peroxidase; LGD - low grade dysplasia; SDS - sodium dodecyl sulfate*Part of this work has been accepted as a poster presentation at the Digestive Disease Week (DDW) meeting, Chicago, IL, USA May 3-6, 2014

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Endoscopic Surveillance Practice for Barrett's Oesophagus in Scotland and Early Experience in Implementing Local Guidelines

Scottish Medical Journal ◽

10.1177/003693300304800205 ◽

2003 ◽

Vol 48 (2) ◽

pp. 43-45 ◽

Cited By ~ 2

Author(s):

E F Shen ◽

S Gladstone ◽

G Milne ◽

S Paterson-Brown ◽

I D Penman

Keyword(s):

Early Experience ◽

High Grade Dysplasia ◽

Low Grade ◽

High Grade ◽

Wide Variability ◽

Low Grade Dysplasia ◽

Surveillance Practice ◽

Four Quadrant ◽

The Impact

Management of columnar lined oesophagus (CLO; Barrett s oesophagus) is controversial. We prospectively audited surveillance practices in Scotland and prospectively assessed the impact of introducing local guidelines for Barrett s surveillance in Edinburgh. Most respondents were gastroenterologists. The majority take random, not four quadrant, biopsies from the CLO. In Edinburgh during 2000, 80 patients underwent surveillance. The guideline protocol was not followed in 30 (37.5%) patients. Follow up of patients without dysplasia generally conformed to the guidelines. Follow up of patients with low grade dysplasia was highly variable while management of those with high grade dysplasia followed the guidelines. Overall we found a wide variability in the management and surveillance of CLO. Early experience suggests that implementation of guidelines is helpful but there is still variation in practice.

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Persistent confirmed low-grade dysplasia in Barrett's esophagus is a risk factor for progression to high-grade dysplasia and adenocarcinoma in a US Veterans cohort

Diseases of the Esophagus ◽

10.1093/dote/doz061 ◽

2019 ◽

Cited By ~ 2

Author(s):

K Y Song ◽

A J Henn ◽

A A Gravely ◽

H Mesa ◽

S Sultan ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Independent Risk Factor ◽

High Grade Dysplasia ◽

Low Grade ◽

High Grade ◽

Increased Risk ◽

Low Grade Dysplasia

SUMMARY Patients with Barrett's esophagus (BE) and low-grade dysplasia (LGD) are at increased risk of esophageal adenocarcinoma (EAC), although many regress to nondysplastic BE. This has significant clinical importance for patients being considered for endoscopic eradication therapy. Our aim is to determine the risk for progression in patients with confirmed persistent LGD. We performed a single-center retrospective cohort study of patients with BE and confirmed LGD between 2006 and 2016. Confirmed LGD was defined as LGD diagnosed by consensus conference with an expert GI pathologist or review by an expert GI pathologist and persistence as LGD present on subsequent endoscopic biopsy. The primary outcome was the incidence rate of HGD (high-grade dysplasia)/EAC. Secondary outcomes included risk factors for dysplastic progression. Risk factors for progression were assessed using univariate and multivariate analysis with logistic regression. Of 69 patients (mean age 65.2 years) with confirmed LGD were included. In total, 16 of 69 patients (23.2%) with LGD developed HGD/EAC during a median follow-up of 3.74 years (IQR, 1.24–5.45). For persistent confirmed LGD, the rate was 6.44 (95% confidence interval (CI), 2.61–13.40) compared to 2.61 cases per 100 patient-years (95% CI, 0.83–6.30) for nonpersistent LGD. Persistent LGD was found in only 29% of patients. Persistent LGD was an independent risk factor for the development of HGD/EAC (OR 4.18; [95% CI, 1.03–17.1]). Persistent confirmed LGD, present in only 1/3 of patients, was an independent risk factor for the development of HGD/EAC. Persistence LGD may be useful in decision making regarding the management of BE.

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Patients With Barrett’s Esophagus and Persistent Low-grade Dysplasia Have an Increased Risk for High-grade Dysplasia and Cancer

Clinical Gastroenterology and Hepatology ◽

10.1016/j.cgh.2015.12.027 ◽

2016 ◽

Vol 14 (7) ◽

pp. 956-962.e1 ◽

Cited By ~ 28

Author(s):

Christine Kestens ◽

G. Johan A. Offerhaus ◽

Jantine W.P.M. van Baal ◽

Peter D. Siersema

Keyword(s):

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

High Grade Dysplasia ◽

Low Grade ◽

High Grade ◽

Increased Risk ◽

Low Grade Dysplasia

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Circumferential Balloon-Based Radiofrequency Ablation of Barrett's Esophagus in Patients with Low-Grade Dysplasia Or High-Grade Dysplasia with and Without a Prior Endoscopic Resection Using the HALO360 Ablation System

Gastrointestinal Endoscopy ◽

10.1016/j.gie.2006.03.237 ◽

2006 ◽

Vol 63 (5) ◽

pp. AB137 ◽

Cited By ~ 4

Author(s):

Jacques J. Bergman ◽

Carine Sondermeijer ◽

Femke P. Peters ◽

Fiebo J. Ten Kate ◽

Paul Fockens

Keyword(s):

Radiofrequency Ablation ◽

Barrett’S Esophagus ◽

Endoscopic Resection ◽

Barrett's Esophagus ◽

High Grade Dysplasia ◽

Low Grade ◽

High Grade ◽

Low Grade Dysplasia

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Morphological characteristics of dysplasia in the mucous membrane adjacent to the tumor in intestinal type gastric cancer

CLINICAL AND EXPERIMENTAL MORPHOLOGY ◽

10.31088/cem2021.10.3.47-54 ◽

2021 ◽

Vol 10 (3) ◽

pp. 47-54

Author(s):

L.V. Volkova ◽

Keyword(s):

Gastric Mucosa ◽

Mucous Membrane ◽

High Grade Dysplasia ◽

Intestinal Type ◽

Field Cancerization ◽

Low Grade ◽

Frequency Of Occurrence ◽

High Grade ◽

Resection Line ◽

Low Grade Dysplasia

Introduction. Despite a significant number of publications and a concept known as Correa’s cascade, dysplas-tic processes and the mechanisms of gastric carcinogenesis, are still far from being completely understood. Dysplasia and the processes in the mucous membrane adjacent to the tumor node, their significance, and their role in the field cancerization have also been studied insufficiently. The aim of this work was to analyze the frequency of occurrence and some characteristics of high- and low-grade dysplasia in the gastric mucosa at variable distances from the tumor node. Materials and methods. We carried out a prospective histological study of surgical specimens from 49 patients with intestinal type gastric adenocarcinoma. We studied tissues from the tumor node and adjacent gastric mucosa at various distances from the tumor and assessed the frequency of occurrence and some characteristics of low- and high-grade dysplasia. Results. In the mucous membrane adjacent to the intestinal type adenocarcinoma, 73.5% of cases demon-strated low- and high-grade dysplasia. In all cases, background and precancerous processes were found in areas adjacent to the tumor node with low- and high-grade dysplasia. Conclusion. The incidence of low- and high-grade dysplasia detected in the mucous membrane adjacent to intestinal type gastric adenocarcinoma significantly decreases as the distance from the tumor node in-creases. Dysplastic changes are associated with epithelial hyperplasia, intestinal metaplasia, and inflamma-tory and atrophic changes. The results obtained support field cancerization and highlight the need to study morphological, molecular, and genetic alterations in the gastric mucosa adjacent to the tumor more deeply. The dysplastic changes present at the resection line area indicate that this fact must be considered when determining the resection line. Keywords: gastric cancer, low-grade dysplasia, high-grade dysplasia, epithelial dysplasia, intestinal meta-plasia, inflammatory infiltration, atrophy

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