Sipos Ferenc, Molnár Béla, Zágoni Tamás, Miheller Pál, Tulassay Zsolt
Semmelweis Egyetem, Altalános Orvostudományi Kar, II Belgyógyászati Klinika, Magyar Tudományos Akadémia, Budapest.
Orv Hetil. 2006 Sep 24;147(38):1835-41.
The risk of colorectal carcinoma development is elevated in chronic, longstanding ulcerative colitis. The changes of such regenerative and immortalizing pathways caused by the inflammatory process that are proved to be carcinogenic in other human tissues have not been fully and uniformly described. Aim of the study was to describe the expression alterations of regenerative signal receptors and cell aging inhibitory systems within colonic crypts considering the histological activity of the disease.
I-type insulin-like growth factor receptor (IGF1R), hepatocyte derived growth factor receptor (HGFR), telomerase reverse transcriptase (TERT) and telomerase associated protein (TP-1) expression were evaluated immunohistochemically on formalin fixed paraffin embedded biopsy specimen from 10 mild, 10 moderate, and 10 severe active inflammation of ulcerative colitis and from 10 normal colonic tissue.
In mild inflammation all observed parameter showed significantly elevated protein expression in protein level compared to normal (p <0.005). In moderately active inflammation only IGF1R expression was significantly higher compared to normal and to mild inflammation (p <0.005). There were no regenerative signal expression alteration in severe inflammation compared to normal, and epithelial telomerase expression was not detectable in these cases.
The expression of regenerative signal receptors and immortalizing factors is elevated in mildly (and moderately) inflamed ulcerative colitis. This phenomenon let the genetically defected epithelial cells to pathologically survive and proliferate, so thus favours the development of tumors.
在慢性、长期溃疡性结肠炎中,结直肠癌发生风险升高。炎症过程引起的此类再生和永生化途径的变化在其他人体组织中被证明具有致癌性,但尚未得到充分且一致的描述。本研究的目的是根据疾病的组织学活性描述结肠隐窝内再生信号受体和细胞衰老抑制系统的表达改变。
采用免疫组织化学方法评估10例轻度、10例中度和10例重度活动期溃疡性结肠炎以及10例正常结肠组织的福尔马林固定石蜡包埋活检标本中I型胰岛素样生长因子受体(IGF1R)、肝细胞衍生生长因子受体(HGFR)、端粒酶逆转录酶(TERT)和端粒酶相关蛋白(TP - 1)的表达。
与正常组织相比,在轻度炎症中,所有观察参数在蛋白水平均显示蛋白表达显著升高(p <0.005)。在中度活动期炎症中,仅IGF1R表达与正常组织和轻度炎症相比显著更高(p <0.005)。与正常组织相比,重度炎症中无再生信号表达改变,且在这些病例中未检测到上皮端粒酶表达。
在轻度(和中度)炎症性溃疡性结肠炎中,再生信号受体和永生化因子的表达升高。这种现象使基因缺陷的上皮细胞能够病理性存活和增殖,从而有利于肿瘤的发生发展。