Expression of apoptosis related proteins during malignant progression in chronic ulcerative colitis.
BACKGROUND
Chronic ulcerative colitis (CUC) is associated with increased risk of developing colon cancer through a dysplasia (intraepithelial neoplasia)-carcinoma sequence.


OBJECTIVE
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.


CONCLUSIONS
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.
van der Woude
C J
CJ
Departments of Gastroenterology and Hepatology, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands. c.vanderwoude@erasmusmc.nl
Moshage
H
H
Homan
M
M
Kleibeuker
J H
JH
Jansen
P L M
PL
van Dekken
H
H
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D003110:Colonic Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2; D018450:Disease Progression; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051020:bcl-X Protein; D019014:fas Receptor / Q000378:metabolism
C494811:BCL2L1 protein, human; D018836:Inflammation Mediators; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D019014:fas Receptor; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases