Prognostic significance of matrix metalloproteinases-1,-2,-7 and-13 and tissue inhibitors of metalloproteinases-1,-2,-3 and-4 in colorectal cancer
Prognostic significance of matrix metalloproteinases-1,-2,-7 and-13 and tissue inhibitors of metalloproteinases-1,-2,-3 and-4 in colorectal cancer
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DOI：
10.1002/ijc.22747
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发表时间：
2007-08-15
影响因子：
6.4
通讯作者：
Laato, Matti
中科院分区：
文献类型：
--
作者：
Hilska, Marja;Roberts, Peter J.;Laato, Matti
许多基质金属蛋白酶（MMPs）的强表达与结直肠癌（CRC）患者的低生存率有关。金属蛋白酶组织抑制剂（TIMPs）的表达与有益和不良的预后相关，因此有必要进一步阐明MMPs和TIMPs在结直肠癌中的意义。评估4个MMPs和TIMPs在结直肠癌中的预后意义。选取351例Dukes A-D期原发性结肠癌或直肠癌患者，经甲醛固定、石蜡包埋组织排列，免疫组化染色MMP-1、-2、-7和-13，以及TIMP-1、-2、-3和-4。恶性上皮及周围间质中MMP-2的高表达与结肠癌患者的生存率降低有关。在直肠癌患者中，强烈的上皮和基质细胞质染色与更长的生存期相关，并且在这里，评估染色程度的观察者间差异低于上皮染色。强基质细胞质染色TIMP-4预测直肠癌患者更长的生存期。多因素分析显示基质细胞质TIMP-3染色是唯一具有独立预后价值的标志物。MMP-2可能是结肠癌的有用预后标志物，TIMP-3和TIMP-4可能是直肠癌的有用预后标志物，但与基质染色相关的发现应谨慎解释。不同的生物学行为或不同的遗传发育可以解释结肠癌和直肠癌之间MMP-2、TIMP-3和TIMP-4表达的差异。(c) 2007 Wiley-Liss, Inc。
Strong expression of many matrix metalloproteinases (MMPs) has been related to poor survival of colorectal cancer (CRC) patients. The expression of tissue inhibitors of metalloproteinases (TIMPs) has been associated with both a beneficial and a poor outcome and there is thus a need to further clarify the Significance of MMPs and TIMPs in CRC. The prognostic significance of 4 MMPs and TIMPs in CRC was evaluated. Formalinfixed, paraffin-embedded tissue arrayed samples of 351 patients with primary colon or rectal cancer of Dukes' stages A-D were selected for immunohistochemical staining of MMP-1, -2, -7 and -13, and TIMP-1, -2, -3 and -4. High expression of MMP-2 in the malignant epithelium as well as in the surrounding stroma was associated with reduced survival of colon cancer patients. Strong epithelial and stromal cytoplasmic staining of TIMP-3 was associated with a longer survival in rectal cancer patients, and here the interobserver variation for evaluating the degree of staining was lower than for epithelial staining. Strong stromal cytoplasmic staining of TIMP-4 predicted longer survival of rectal cancer patients. Multivariate analysis showed that stromal cytoplasmic TIMP-3 staining was the only marker of independent prognostic value. MMP-2 might be a useful prognostic marker in colon cancer, and TIMP-3 and TIMP-4 in rectal cancer, but the findings associated with stromal staining should be interpreted with some caution. Different biologic behavior or different genetic development may explain the differences between colon and rectal cancers regarding the expression of MMP-2, TIMP-3 and TIMP-4. (c) 2007 Wiley-Liss, Inc.