Original Article
Immunohistochemistry in the diagnosis of dysplasia in chronic inflammatory bowel disease colorectal polyps

https://doi.org/10.1016/j.ajg.2016.06.003Get rights and content

Abstract

Background and study aims

Development of cancer is the most significant complication in inflammatory bowel disease (IBD). Distinguishing true dysplasia from reactive atypia in polyps is difficult, leading sometimes to the unsatisfactory diagnosis of “indefinite for dysplasia”. Therefore, there is a need for the development of markers that can help improve diagnosis.

We evaluated the diagnostic value of the expression of AMACR, Ki67 and p53 by immunohistochemistry in the diagnosis of dysplasia in polyps developed on IBD.

Patients and methods

Forty colorectal polyps in IBD were studied. These had been diagnosed over a period of 11 years. Dysplasia was classified according to the Vienna Classification (version 2000). Immunohistochemistry was performed using anti-AMACR, anti-Ki67 and anti-p53 antibodies.

Results

Polyps were classified as follows: 21 negative for dysplasia (ND), 10 indefinite for dysplasia (IFD), 6 low-grade dysplasia (LGD), 1 high-grade dysplasia (HGD) and 2 adenocarcinomas (ACA).

AMACR positivity was observed in all polyps with HGD and ACA, 5 of the 6 LGD polyps and 3 of the 10 IFD (p = 0.007).

p53 immunostaining showed nuclear staining in the basal part of the crypts in 8 of the 10 IFD lesions. In ACA and HGD polyps, p53 positivity was typically observed in all epithelial cell layers (p = 0.004).

ACA and HGD showed diffuse and scattered staining of Ki67 along the full length of the crypts. Five lesions with LGD had extension of Ki-67 positive cells up to and into the surface epithelium. Ki67 staining in all IFD lesions was restricted to the basal third of the crypt (p < 0.001).

By combining the three markers, a relationship with dysplasia was statistically significant (p < 0.001). Sensitivity ranged from 66.7% to 88.9% and specificity from 71.4% to 100%.

The positive predictive value (PPV) for detecting dysplasia using these different antibodies ranged from 66.7% to 100% and the negative predictive value (NPV) for excluding dysplasia ranged from 85.7% to 93.3%.

Conclusions

The high degree of sensitivity and specificity of AMACR, p53 and Ki67 for dysplasia in IBD suggests that these antibodies, when combined, may be useful to detect neoplastic epithelium in this condition.

Introduction

Extensive and long standing inflammatory bowel disease (IBD) is well known to predispose patients to the development of colorectal carcinoma. This cancer is preceded by dysplasia, sometimes with polypoid appearance. On the basis of morphologic criteria, dysplasia is classified into 1 of 5 categories according to the Vienna classification: Negative for dysplasia (ND), indefinite for dysplasia (IFD), low-grade dysplasia (LGD), high-grade dysplasia (HGD) and adenocarcinoma (ACA) [1].

Differentiating between regenerative changes and true dysplasia in the IFD category is often difficult even in absence of active inflammation and even for experienced pathologists [2]. A search for more objective methods to identify early neoplastic changes in the epithelium therefore seems warranted.

Immunohistochemistry would solve this problem by revealing an expression of potential marker of neoplastic cells, alpha-methylacyl coenzyme A racemase (AMACR) [3], the proliferation index (Ki-67) [4] and of the tumour suppressor protein, p53 [3].

The aim of our study was to evaluate the diagnostic value of the expression of AMACR, Ki67 and p53 in the diagnosis of dysplasia in IBD.

Section snippets

Patients and methods

Our study included all colorectal polyps from patients with IBD selected by a retrospective search through the files of Department of Pathology of Habib Thameur Hospital in Tunis, throughout a period of 11 years between 2001 and 2011.

It included both biopsy and polyps removed from colectomy specimens. Fragmented and / or crushed polyps, and those which are difficult to analyse histologically were excluded. Clinicopathological parameters including the age and gender of the patients, the type of

Results

Forty polyps were removed in 21 patients with IBD of mean age of 47.5 ± 14.9 years (range: 23–75 years). The male:female ratio was 1.62. Amongst the polyps, 34 were from 16 patients with ulcerative colitis and 6 were obtained from 5 patients with Crohn’s disease. The duration of disease progression varied from several days to 31 years. It was less than 10 years in 55% of cases and between 10 and 25 years in 32% of cases. The median size of colorectal polyps was 7 mm (range 3–20 mm). It was less than 10 

Discussion

In our study, we have investigated whether AMACR, Ki67 and p53 immunostaining might help in the diagnosis of dysplasia in IBD developed polyps.

We have obtained substantial expression changes in the majority of dysplastic polyps. These findings raise the possibility that some of these changes may also be useful in a diagnostic setting. Most dysplastic and cancerous polyps showed high AMACR expression (p = 0.007). Extension of p53 and Ki67 staining into the upper third of the crypts was found in

Conflict of interest

The authors declared that there was no conflict of interest.

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© 2016 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.