Expression of apoptosis related proteins during malignant progression in chronic ulcerative colitis

• Published in: Journal of clinical pathology Vol. 58; no. 8; pp. 811 - 814
• Main Authors: van der Woude, C J, Moshage, H, Homan, M, Kleibeuker, J H, Jansen, P L M, van Dekken, H
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and Association of Clinical Pathologists 01.08.2005; BMJ; BMJ Publishing Group LTD; Copyright 2005 Journal of Clinical Pathology
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Apoptosis; bcl-X Protein; Biological and medical sciences; carcinoma; Caspase 3; Caspases - metabolism; Cell growth; chronic ulcerative colitis; Colitis, Ulcerative - complications; Colitis, Ulcerative - metabolism; Colitis, Ulcerative - pathology; Colonic Neoplasms - etiology; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Colorectal cancer; COX-2; Cyclooxygenase 2; Disease Progression; Endoscopy; fas Receptor - metabolism; Female; Gastroenterology. Liver. Pancreas. Abdomen; Histology; Humans; inducible nitric oxide synthase; Inflammation; Inflammation Mediators - metabolism; Inflammatory bowel disease; iNOS; Investigative techniques, diagnostic techniques (general aspects); Laboratories; LOH; loss of heterozygosity; Male; Medical sciences; Membrane Proteins; Middle Aged; Mutation; Neoplasm Proteins - metabolism; NF-κB; Nitric oxide; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type II; nuclear factor κB; Original; Other diseases. Semiology; Pathogenesis; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Precancerous Conditions - metabolism; Precancerous Conditions - pathology; Prostaglandin-Endoperoxide Synthases - metabolism; Proteins; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rodents; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; ulcerative colitis; California; Anatomic pathology; Chronic; Cell death; Malignant transformation; Digestive diseases; Intestinal disease; Protein; Inflammatory disease; Apoptosis; Ulcerative colitis
• ISSN: 0021-9746; 1472-4146
• DOI: 10.1136/jcp.2004.017418

Background: Chronic ulcerative colitis (CUC) is associated with increased risk of developing colon cancer through a dysplasia (intraepithelial neoplasia)–carcinoma sequence. Aims: To investigate the expression of apoptosis and inflammatory related proteins in CUC. Methods: The expression of proteins involved in apoptosis and inflammation (inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), Bcl-xl, Fas, and active caspase 3) was investigated and compared with that seen in sporadic colon carcinoma. Results: COX-2 was negative in the epithelium of all samples. iNOS was clearly present in inflammatory areas in CUC epithelium, weakly expressed in dysplasia, and absent or weakly expressed in tumour cells. Bcl-xl was absent in CUC, increased in dysplasia, and highly expressed in most carcinomas. Fas expression was positive in the surface epithelium of CUC, dysplasia, and most tumour cells. Activated caspase 3 was weakly positive in all samples, indicating limited apoptosis. Compared with CUC associated carcinoma, iNOS was consistently expressed in sporadic colon carcinoma cells, whereas Bcl-xl was almost absent in these tumour cells and Fas was only weakly expressed. Activated caspase 3 was present in normal mucosal samples and some tumour cells. Conclusion: Apoptosis related proteins—particularly iNOS, Bcl-xl, and Fas—show a distinct pattern of expression in the CUC to carcinoma sequence, which differs from that seen in sporadic carcinoma, but bears a striking resemblance to that seen during neoplastic progression in Barrett’s oesophagus. These results support a causal role for chronic inflammation in cancer development in CUC, and treatment of ulcerative colitis should aim to minimise inflammation.