Klinge U, Rosch R, Junge K, Krones C J, Stumpf M, Lynen-Jansen P, Mertens P R, Schumpelick V
Department of Surgery of the RWTH-Aachen, RWTH-Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany,
Int J Colorectal Dis. 2007 May;22(5):515-20. doi: 10.1007/s00384-006-0199-1. Epub 2006 Oct 5.
The extracellular matrix and the interactive signalling between its components are thought to play a pivotal role for tumour development and metastasis formation. An altered matrix composition as potential underlying pathology for the development of colorectal cancer was hypothesized.
In a retrospective study of patients with colon cancer, the extracellular matrix in tumour-free bowel specimen was investigated in comparison with non-infected bowel specimen from patients operated on for colonic diverticulosis. The following matrix parameters with known associations to tumour formation, cell proliferation, invasion and metastasis were analysed by immunohistochemistry and quantified by a scoring system: VEGF, TGF-beta, ESDN, CD117, c-erb-2, cyclin D1, p53, p27, COX-2, YB-1, collagen I/III, MMP-13, PAI and uPAR. Expression profiles and correlations were calculated.
The comparison of the two groups revealed a significantly decreased immunostaining for CD117 and TGF-beta in the cancer group (8.5+/-2.6 vs 10.3+/-2,1 and 4.9+/-1.5 vs 8.1+/-3, respectively), whereas PAI scores were significantly higher than in patients with diverticular disease (8.1+/-1.6 vs 6.2+/-0.9). Overall correlation patterns of matrix parameters indicated pronounced differences between tumour-free tissue in cancer patients compared with patients with diverticular disease.
Our results indicate distinct differences in the colonic tissue architecture between cancer patients and patients with diverticulitis that support the notion of an altered matrix composition predisposing to the development of colon cancer.
细胞外基质及其成分之间的相互作用信号被认为在肿瘤发展和转移形成中起关键作用。有人提出，基质组成改变可能是结直肠癌发生的潜在病理基础。
在一项对结肠癌患者的回顾性研究中，将无肿瘤肠组织标本中的细胞外基质与因结肠憩室病接受手术的患者的未感染肠组织标本进行比较。通过免疫组织化学分析以下与肿瘤形成、细胞增殖、侵袭和转移有已知关联的基质参数，并通过评分系统进行量化：血管内皮生长因子（VEGF）、转化生长因子-β（TGF-β）、内皮抑素（ESDN）、CD117、c-erb-2、细胞周期蛋白D1、p53、p27、环氧合酶-2（COX-2）、YB-1、Ⅰ/Ⅲ型胶原、基质金属蛋白酶-13（MMP-13）、纤溶酶原激活物抑制剂（PAI）和尿激酶型纤溶酶原激活物受体（uPAR）。计算表达谱和相关性。
两组比较显示，癌症组中CD117和TGF-β的免疫染色显著降低（分别为8.5±2.6对10.3±2.1和4.9±1.5对8.1±3），而PAI评分显著高于憩室病患者（8.1±1.6对6.2±0.9）。基质参数的总体相关模式表明，癌症患者的无肿瘤组织与憩室病患者之间存在明显差异。
我们的结果表明，癌症患者与憩室炎患者的结肠组织结构存在明显差异，这支持了基质组成改变易导致结肠癌发生的观点。
