Leinonen Tero, Pirinen Risto, Böhm Jan, Johansson Risto, Kosma Veli-Matti
Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Kuopio and Kuopio University Hospital, Kuopio, Finland.
Histol Histopathol. 2008 Jun;23(6):693-700. doi: 10.14670/HH-23.693.
The purpose of this study was to analyse the expression of matrix metalloproteinase-2 (MMP-2) and its extracellular matrix metalloproteinase inducer (EMMPRIN) in non-small cell lung cancer (NSCLC), and to evaluate their significance to predict tumour behaviour. The study consists of 212 patients treated by the resection of the tumour. Tumour samples were stained immunohistochemically, and the expression of MMP-2 and EMMPRIN was evaluated both in tumour cells and in peritumoural stromal tissue. The results were compared with clinicopathological factors and survival of the patients. High expression of MMP-2 in tumour cells was found in 83 out of 191 cases (44%). Adenocarcinomas showed more often high expression of MMP-2 as compared with squamous cell or large cell carcinomas (p=0.001). High cancer cell associated MMP-2 expression was associated with increased tumour recurrence (p=0.001). Tumour stroma showed positive staining in 162 (98%) cases and was considered highly stained in 120 (72%) cases. The high stromal MMP-2 expression was noticed more often among large cell carcinomas as compared with other histological types (p=0.007). High cancer cell associated EMMPRIN expression was found in 115 (61%) cases and was associated only with high MMP-2 expression in tumour cells (p=0.006). In overall survival (OS) and disease free survival (DFS) analyses, type of tumour (p=0.001 and p=0.0004), advanced stage (p=0.001 and p=0.013) and high MMP-2 expression in tumour cells (p=0.018 and p=0.001) were associated with poor survival. Also, high stromal MMP-2 expression was related to poor outcome in both OS and DFS analyses (p=0.010 and 0.045, respectively). In multivariate analysis, stromal MMP-2 expression retained its prognostic value to predict OS and DFS (p=0.028 and p=0.039, respectively), together with tumour type and stage (p=0.017, p=0.001 and p=0.021, p=0.008, respectively). The present study shows the significant prognostic value of MMP-2 in NSCLC suggesting that the use of MMP-2 is valuable in determining the patients with more aggressive disease.
本研究旨在分析基质金属蛋白酶-2（MMP-2）及其细胞外基质金属蛋白酶诱导剂（EMMPRIN）在非小细胞肺癌（NSCLC）中的表达，并评估其对预测肿瘤行为的意义。该研究纳入了212例接受肿瘤切除术的患者。对肿瘤样本进行免疫组织化学染色，评估肿瘤细胞和肿瘤周围基质组织中MMP-2和EMMPRIN的表达。将结果与患者的临床病理因素及生存情况进行比较。191例病例中有83例（44%）肿瘤细胞中MMP-2高表达。与鳞状细胞癌或大细胞癌相比，腺癌中MMP-2高表达更为常见（p=0.001）。肿瘤细胞相关的MMP-2高表达与肿瘤复发增加相关（p=0.001）。肿瘤基质在162例（98%）病例中呈阳性染色，120例（72%）病例被认为染色强。与其他组织学类型相比，大细胞癌中基质MMP-2高表达更为常见（p=0.007）。115例（61%）病例中发现肿瘤细胞相关的EMMPRIN高表达，且仅与肿瘤细胞中MMP-2高表达相关（p=0.006）。在总生存（OS）和无病生存（DFS）分析中，肿瘤类型（p=0.001和p=0.0004）、晚期（p=0.001和p=0.013）以及肿瘤细胞中MMP-2高表达（p=0.018和p=0.001）与生存不良相关。此外，在OS和DFS分析中，基质MMP-2高表达也与不良预后相关（分别为p=0.010和0.045）。在多变量分析中，基质MMP-2表达与肿瘤类型和分期一起，对预测OS和DFS仍具有预后价值（分别为p=0.028和p=0.039，以及p=0.017、p=0.001和p=0.021、p=0.008）。本研究显示MMP-2在NSCLC中具有显著的预后价值，提示MMP-2的检测对于确定疾病侵袭性更强的患者具有重要价值。
