van Dekken Herman, Wink Josiane C, Vissers Kees J, Franken Patrick F, Ruud Schouten W, J Hop Wim C, Kuipers Ernst J, Fodde R, Janneke van der Woude C
Department of Pathology, Erasmus Medical Center, Dr. Molewaterplein 50, 3015GE Rotterdam, The Netherlands.
Acta Histochem. 2007;109(4):266-72. doi: 10.1016/j.acthis.2007.02.007. Epub 2007 Apr 18.
Long-standing ulcerative colitis (UC) has been associated with a high risk of developing colonic adenocarcinoma. Importantly, both low- and high-grade dysplasia are strongly related to the presence or development of malignancy. The canonical Wnt/beta-catenin signaling pathway is of crucial importance in cancer development and progression, but its role in UC-related carcinogenesis remains to be determined. We evaluated the immunolabeling patterns of beta-catenin, as well as the products of Wnt-associated cancer genes E-cadherin, cyclin D1 and c-myc, along the dysplasia-carcinoma pathway in UC. For this purpose, immunohistochemistry (IHC) was performed on 18 adenocarcinomas and 17 dysplasias, derived from 21 patients. We found that intracellular beta-catenin accumulation, the hallmark of Wnt signaling activation, is observed in dysplasia, together with enhanced labeling of nuclear protein cyclin D1 and reduction of membranous labeling of E-cadherin. c-myc displayed moderate immunolabeling in the (pre)malignant lesions. Thus, the Wnt pathway is activated in early stages of malignant progression in UC. Furthermore, upregulation of the oncogene cyclin D1 and downregulation of tumor suppressor E-cadherin also occurs in the (pre)neoplastic state. This may contribute to the high potential for malignant degeneration of dysplasia in UC-related colitis.
长期溃疡性结肠炎（UC）与发生结肠腺癌的高风险相关。重要的是，低级别和高级别发育异常均与恶性肿瘤的存在或发展密切相关。经典的Wnt/β-连环蛋白信号通路在癌症发生和进展中至关重要，但其在UC相关癌变中的作用仍有待确定。我们评估了β-连环蛋白的免疫标记模式，以及Wnt相关癌基因E-钙黏蛋白、细胞周期蛋白D1和c-myc的产物在UC发育异常-癌转变途径中的情况。为此，对来自21例患者的18例腺癌和17例发育异常进行了免疫组织化学（IHC）检测。我们发现，在发育异常中观察到细胞内β-连环蛋白积累，这是Wnt信号激活的标志，同时核蛋白细胞周期蛋白D1的标记增强，E-钙黏蛋白的膜标记减少。c-myc在（癌）前病变中显示出中度免疫标记。因此，Wnt通路在UC恶性进展的早期阶段被激活。此外，癌基因细胞周期蛋白D1的上调和肿瘤抑制因子E-钙黏蛋白的下调也发生在（癌）前状态。这可能有助于解释UC相关结肠炎中发育异常的高恶性转化潜能。
