Evaluation of the immunoexpression of COX-1, COX-2 and p53 in Crohn's disease.
BACKGROUND
Crohn's disease accompanied by nonspecific or idiopathic ulcerative proctocolitis corresponds to a condition called intestinal inflammatory disease. The immunoexpression of cyclooxygenase 2 (COX-2) in Crohn's disease becomes more marked with progression of the disease and the presence of wild-type p53 suppresses the transcription of COX-2.


OBJECTIVE
To investigate the immunoexpression of cyclooxygenase 1 (COX-1), COX-2 and p53 in Crohn's ileocolitis and to correlated this expression with clinical and histopathological parameters.


METHODS
Forty-five cases of Crohn's disease, 16 cases of actinic colitis (diseased-control group) and 11 cases without a history of intestinal disease (normal control group) were studied. Hematoxylin-eosin-stained sections were submitted to histopathological analysis and the immunohistochemical expression of COX-1, COX-2 and p53 was evaluated by the streptavidin-biotin-peroxidase method.


RESULTS
Sixty percent of the Crohn's disease patients were women and 40% were men, with 75.5% whites and 25.5% non-whites. The disease involved the terminal ileum in 44.5% of cases, ileum in 33.3%, colon in 20% and duodenum-ileum in 2.2%. A significant association was observed between COX-2 immunoreactivity and age < or =40 years. Histopathological analysis of Crohn's disease samples showed mild or moderate crypt distortion (57.8% and 35.6% of cases), atrophy (6.6%), mild, moderate and marked chronic inflammation (46.7%, 26.7% and 20%), acute inflammatory activity (93.3%), ulceration (24.4%), mucin depletion (37.8%), Paneth's cells (24.4%), intraepithelial lymphocytes (93.3%), and subepithelial collagen (6.7%). In the CD group, COX-1 immunoreactivity in epithelial and inflammatory cells was observed in 26.7% and 22.2% of cases, respectively. COX-2 immunoreactivity was detected in epithelial cells in 68.9% of cases and in inflammatory cells in 46.7%. A marginal difference in COX-2 reactivity was observed between epithelial and inflammatory cells in association with acute inflammatory activity and increase in intraepithelial lymphocytes. Comparison of the date among the threes groups (Crohn's disease, actinic colitis and normal controls) showed a higher proportion of cases presenting COX-2 immunoreactivity in inflammatory cells in the Crohn's disease group. No p53 reactivity was observed in all cases.


CONCLUSIONS
COX-2 immunoexpression is high in Crohn's disease, which suggest a possible role of the protein in the pathogenesis of the inflammation. The absence of epithelial dysplasia in all Crohn's disease samples was correlated with the lack of expression of p53.
Romero
Mônica
M
Departament of Pathology, Paulista Medical School, Federal University of São Paulo State, São Paulo, SP, Brasil.
Artigiani
Ricardo
R
Costa
Henrique
H
Oshima
Celina Tizuko Fujiyama
CT
Miszputen
Sender
S
Franco
Marcello
M
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000201:enzymology / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D003424:Crohn Disease / Q000201:enzymology / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007079:Ileitis / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011878:Radiotherapy / Q000009:adverse effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D055815:Young Adult
D016159:Tumor Suppressor Protein p53; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2