Institute of Clinical Medicine, University of Tromso, Norway.
Lung Cancer. 2012 Feb;75(2):235-41. doi: 10.1016/j.lungcan.2011.06.010. Epub 2011 Jul 18.
Matrix metalloproteinases (MMPs) are considered important players in angiogenesis and cancer progression. Several drugs developed for targeting MMPs have until now been without clinical efficacy. As both malignant cells and cells of the surrounding stroma contribute to tumor growth, we have explored the impact of MMP-2, -7 and -9 expression in both the tumor and stromal compartment of non-small-cell lung cancers (NSCLC).
From 335 unselected stage I to IIIA NSCLC carcinomas, duplicate tumor and tumor-associated stromal cores were collected in tissue microarrays (TMAs). Immunohistochemistry was used to detect the expression of MMP-2, -7 and -9 in tumor and stromal cells.
In univariate analyses, high tumor cell MMP-7 expression (P=0.029) and high stromal MMP-9 expression (P=0.001) were positive prognostic factors. In the multivariate analysis, high tumor cell MMP-7 expression (HR 1.58, CI 1.08-2.32, P=0.020) and high stromal MMP-9 expression (HR 1.92, CI 1.25-2.96, P=0.003) were independent positive prognostic factors for disease-specific survival.
High levels of MMP-7 in tumor cells and high levels of MMP-9 in tumor associated stroma were independent positive prognostic factors in NSCLC patients.
基质金属蛋白酶（MMPs）被认为是血管生成和癌症进展中的重要参与者。迄今为止，已有几种针对 MMP 开发的药物没有临床疗效。由于恶性细胞和周围基质细胞都有助于肿瘤生长，我们研究了 MMP-2、-7 和 -9 在非小细胞肺癌（NSCLC）的肿瘤和基质区室中的表达。
从 335 例未经选择的 I 期至 IIIA 期 NSCLC 癌中，在组织微阵列（TMA）中收集重复的肿瘤和肿瘤相关的基质核心。免疫组织化学用于检测 MMP-2、-7 和 -9 在肿瘤和基质细胞中的表达。
在单因素分析中，高肿瘤细胞 MMP-7 表达（P=0.029）和高基质 MMP-9 表达（P=0.001）是阳性预后因素。在多因素分析中，高肿瘤细胞 MMP-7 表达（HR 1.58，CI 1.08-2.32，P=0.020）和高基质 MMP-9 表达（HR 1.92，CI 1.25-2.96，P=0.003）是 NSCLC 患者疾病特异性生存的独立阳性预后因素。
肿瘤细胞中 MMP-7 水平高和肿瘤相关基质中 MMP-9 水平高是非小细胞肺癌患者的独立阳性预后因素。
