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Significant correlation of morphological remodeling in ulcerative colitis with disease duration and between elevated p53 and p21 WAF1 expression in rectal mucosa and neoplastic development
Author(s) -
Mitsuhashi Jun,
Mikami Tetuo,
Saigenji Katsunori,
Okayasu Isao
Publication year - 2005
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/j.1440-1827.2005.01802.x
Subject(s) - ulcerative colitis , pathology , inflammation , immunohistochemistry , biology , disease , medicine
Although a chronic inflammation‐carcinoma sequence has been proposed in cases of longstanding ulcerative colitis (UC), the relationship of morphological alteration or remodeling of regenerated mucosa to carcinoma development is yet to be clarified. Therefore, mucosae of 49 resected rectae from individuals with UC were histologically and quantitatively analyzed, with regard to thickness and morphological parameters of crypts, in relation to the disease duration, clinical disease activity and neoplastic development. An immunohistochemical examination of Ki‐67, p53, p21 WAF1 and ssDNA labeling was also included. Significant correlations of number, height, angle, fusion and Paneth cell metaplasia of crypts, as well as thickness of the muscularis mucosae, were revealed with disease duration, as confirmed by three‐dimensional reconstructed image analysis. p53 and p21 WAF1 ‐positive cells increased with disease duration and were significantly more frequent in cases with neoplasia, suggesting more DNA damage. However, this was not the case for ssDNA labeling, assessed as an indicator of apoptosis. In general, histological changes and p53, p21 WAF1 and Ki‐67 labeling were correlated. In conclusion, histological parameters for mucosal remodeling correlate well with UC duration, indicating accumulation of structural alterations. Accumulated damage to DNA, reflected by increased p53 and p21 WAF1 labeling indices, might be involved in cancer development, as well as longstanding inflammation.