Marx, A. et al. Combined alpha-methylacyl coenzyme A racemase/p53 analysis to identify dysplasia in inflammatory bowel disease. Hum. Pathol. 40, 166-173
Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. Human pathology
(Impact Factor: 2.77).
10/2008; 40(2):166-73. DOI: 10.1016/j.humpath.2008.06.027
Identification of dysplasia in inflammatory bowel disease represents a major challenge for both clinicians and pathologists. Clear diagnosis of dysplasia in inflammatory bowel disease is sometimes not possible with biopsies remaining "indefinite for dysplasia." Recent studies have identified molecular alterations in colitis-associated cancers, including increased protein levels of alpha-methylacyl coenzyme A racemase, p53, p16 and bcl-2. In order to analyze the potential diagnostic use of these parameters in biopsies from inflammatory bowel disease, a tissue microarray was manufactured from colons of 54 patients with inflammatory bowel disease composed of 622 samples with normal mucosa, 78 samples with inflammatory activity, 6 samples with low-grade dysplasia, 12 samples with high-grade dysplasia, and 66 samples with carcinoma. In addition, 69 colonoscopic biopsies from 36 patients with inflammatory bowel disease (28 low-grade dysplasia, 8 high-grade dysplasia, and 33 indefinite for dysplasia) were included in this study. Immunohistochemistry for alpha-methylacyl coenzyme A racemase, p53, p16 and bcl-2 was performed on both tissue microarray and biopsies. p53 and alpha-methylacyl coenzyme A racemase showed the most discriminating results, being positive in most cancers (77.3% and 80.3%) and dysplasias (94.4% and 94.4%) but only rarely in nonneoplastic epithelium (1.6% and 9.4%; P < .001). Through combining the best discriminators, p53 and alpha-methylacyl coenzyme A racemase, a stronger distinction between neoplastic tissues was possible. Of all neoplastic lesions, 75.8% showed a coexpression of alpha-methylacyl coenzyme A racemase and p53, whereas this was found in only 4 of 700 nonneoplastic samples (0.6%). alpha-methylacyl coenzyme A racemase/p53 coexpression was also found in 10 of 33 indefinite for dysplasia biopsies (30.3 %), suggesting a possible neoplastic transformation in these cases. Progression to dysplasia or carcinoma was observed in 3 of 10 p53/alpha-methylacyl coenzyme A racemase-positive, indefinite-for-dysplasia cases, including 1 of 7 cases without and 2 of 3 cases with p53 mutation. It is concluded that combined alpha-methylacyl coenzyme A racemase/p53 analysis may represent a helpful tool to confirm dysplasia in inflammatory bowel disease.
Available from: ncbi.nlm.nih.gov
Canadian journal of gastroenterology = Journal canadien de gastroenterologie 06/2009; 23(5):345-7. · 1.98 Impact Factor
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ABSTRACT: The risk of developing colorectal cancer in patients with colitis-associated dysplasia is considerable. Surveillance programs in patients with ulcerative colitis and Crohn's disease aim to detect dysplastic lesions early and rely heavily on taking random biopsy samples along the length of the colon. Diagnosing dysplasia can be difficult because of the heterogeneous endoscopic appearance of dysplasia and the poor interobserver agreement among pathologists when grading dysplasia. Colitis-associated dysplasia may present as a dysplasia-associated lesion or mass (DALM), which may be indistinguishable from a sporadic adenoma in non-colitic tissue, or may arise in flat mucosa of endoscopically normal appearance. Information about the endoscopic appearance, the colonic distribution and the histopathological grade of colitis-associated dysplasia is required to define the optimal treatment. This Review summarizes the endoscopic and histopathological features of colitis-associated dysplasia and the requirements for optimal interaction between endoscopists and pathologists, with the aim of reducing the uncertainties in the diagnosis of dysplastic lesions and improving the management of colitis-associated dysplasia.
Nature Reviews Gastroenterology & Hepatology 09/2009; 6(11):671-8. DOI:10.1038/nrgastro.2009.162 · 12.61 Impact Factor
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ABSTRACT: Colorectal cancer, the most lethal long-term complication of chronic inflammatory bowel disease (IBD), is the culmination of a complex sequence of molecular and histologic derangements of the intestinal epithelium that are initiated and at least partially sustained by chronic inflammation. Dysplasia, the earliest histologic manifestation of this process, plays an important role in cancer prevention by providing the first clinical alert that this sequence is underway and serving as an endpoint in colonoscopic surveillance of patients at high risk for colorectal cancer.
To review the histology, nomenclature, clinical implications, and molecular pathogenesis of dysplasia in IBD.
Literature review and illustrations from case material.
The diagnosis and grading of dysplasia in endoscopic surveillance biopsies play a decisive role in the management of patients with IBD. Although interpathologist variation, endoscopic sampling problems, and incomplete information regarding the natural history of dysplastic lesions are important limiting factors, indirect evidence that surveillance may be an effective means of reducing cancer-related mortality in the population with IBD has helped validate the histologic criteria, nomenclature, and clinical recommendations that are the basis of current practice among pathologists and clinicians. Emerging technologic advances in endoscopy may permit more effective surveillance, but ultimately the greatest promise for cancer prevention in IBD lies in expanding our thus far limited understanding of the molecular pathogenetic relationships between neoplasia and chronic inflammation.
Archives of pathology & laboratory medicine 06/2010; 134(6):876-95. DOI:10.1043/1543-2165-134.6.876 · 2.84 Impact Factor
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