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Expression of apoptosis related proteins during malignant progression in chronic ulcerative colitis
  1. C J van der Woude1,
  2. H Moshage2,
  3. M Homan2,
  4. J H Kleibeuker2,
  5. P L M Jansen3,
  6. H van Dekken4
  1. 1Departments of Gastroenterology and Hepatology, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands
  2. 2University Hospital Groningen, 9713 GZ Groningen, The Netherlands
  3. 3Academic Medical Centre, 1100 DD Amsterdam, The Netherlands
  4. 4Department of Pathology, Erasmus MC
  1. Correspondence to:
 Dr C J van der Woude
 Department of Gastroenterology and Hepatology, Erasmus MC/University Medical Centre, Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands;


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.

  • COX-2, cyclooxygenase 2
  • iNOS, inducible nitric oxide synthase
  • LOH, loss of heterozygosity
  • NF-κB, nuclear factor κB
  • UC, ulcerative colitis
  • chronic ulcerative colitis
  • carcinoma
  • apoptosis

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