TITLE

METAPLASTIC PANETH CELLS IN ULCERATIVE COLITIS AND COLORECTAL CANCER

AUTHOR(S)
Osborne, C.L.E.; Khan, A.; Ogunbiyi, O.; Keshav, S.
PUB. DATE
April 2003
SOURCE
Gut;Apr2003 Supplement 1, Vol. 52, pA62
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background and Aims: Paneth cell metaplasia (PCM) in the colon of patients with inflammatory bowel disease (IBD) represents a distinct form of the host inflammatory response. Paneth cells secrete an array of antimicrobial proteins including lysozyme, defensins, and type Ila secretory phospholipase A2, (PLA2-Ila) which lyses bacterial cell membranes, and is also secreted into the circulation as part of the acute phase response. PLA2-IIa levels are higher in the colonic mucosa of patients with severe colitis who are at greater risk of colorectal cancer (CRC), and the PLA2-IIa gene is a modifier of neoplasia in the Min mouse model of familial adenomatous polyposis. We therefore investigated PLA2-lla expression in UC, CRC, and UC-associated CRC, to determine if expression was higher in UC-associated CRC compared to sporadic CRC. Methods: PCM and PLA2-IIa protein expression in paraffin embedded sections of colon from UC, sporadically occurring CRC and UC associated CRC by indirect immunohistochemistry. We compared PLA2-IIa expression with positive (anti-CD45 antibody) and negative controls (secondary antibody only), and used western blot analysis on fresh tissue from paired samples of UC and UC associated CRC, sporadic CRC and normal colon, to confirm the immunohistochemical data. Results: PCM and PLA2-Ila expression were detected in 67% of UC samples, but not in any normal colon. PCM was detected in 30% of UC associated CRC, compared to 6.3% of sporadically occurring CRC. tn the paired tissue samples, PLA2-IIa expression was clearly demonstrated by western blotting in both UC specimens and in one UC associated CRC, but was not in sporadic CRC or normal tissue. Conclusion: PCM in colonic mucosa is easily and reliably identified by the presence PLA2-IIa protein in Paneth cell granules. PCM can be used as an indicator of disease activity in UC and is also a marker of UC associated CRC, where it may play a role in pathogenesis, which remains to be determined.
ACCESSION #
9747705

 

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