Significant correlation of morphological remodeling in ulcerative colitis with disease duration and between elevated p53 and p21WAF1 expression in rectal mucosa and neoplastic development
Significant correlation of morphological remodeling in ulcerative colitis with disease duration and between elevated p53 and p21WAF1 expression in rectal mucosa and neoplastic development
复制标题
DOI：
10.1111/j.1440-1827.2005.01802.x
复制
发表时间：
2005-03-01
影响因子：
2.2
通讯作者：
Okayasu, I
中科院分区：
文献类型：
--
作者：
Mitsuhashi, J;Mikami, T;Okayasu, I
虽然在长期溃疡性结肠炎(UC)的病例中提出了慢性炎症-癌序列，但再生粘膜的形态改变或重塑与肿瘤发生的关系尚不清楚。因此，我们对49例UC患者切除的直肠粘膜进行了组织学和定量分析，包括隐窝的厚度和形态参数，以及与病程、临床疾病活动性和肿瘤发展的关系。免疫组织化学检测Ki-67、P53、p21(WAF1)及单链DNA标记。三维重建图像分析显示，隐窝的数目、高度、角度、融合、Paneth细胞化生以及粘膜肌层厚度与病程密切相关。P53和p21(WAF1)阳性细胞随着病程的延长而增加，在肿瘤病例中明显更常见，提示DNA损伤更多。然而，单链DNA标记的情况并非如此，它被评估为细胞凋亡的指标。组织学改变与p53、p21(WAF1)和Ki-67的表达呈正相关。总之，粘膜重塑的组织学参数与UC病程有很好的相关性，表明结构改变的累积。DNA的累积损伤，反映为p53和p21(WAF1)标记指数的增加，可能参与了癌症的发展，以及长期的炎症。
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.