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

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 11years. 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.

Keywords: Chronic inflammatory bowel disease; Dysplasia; Immunohistochemistry; Polyps.