Expression and prognostic significance of metalloproteinases and their tissue inhibitors in patients with small-cell lung cancer
Expression and prognostic significance of metalloproteinases and their tissue inhibitors in patients with small-cell lung cancer
复制标题
DOI：
10.1200/jco.1999.17.6.1802
复制
发表时间：
1999-06-01
影响因子：
45.3
通讯作者：
Shepherd, FA
中科院分区：
文献类型：
--
作者：
Michael, M;Babic, B;Shepherd, FA
目的：基质金属蛋白酶（MMPs）及其组织抑制剂（TIMPs）在肿瘤的发生、发展中起重要作用。MMP的表达与一些肿瘤的晚期临床分期和低生存率相关，但小细胞肺癌（SCLC）的数据缺乏。本研究的目的是评估MMPs和TIMPs在SCLC中的表达，并评估其相对于标准预后因素的重要性。患者和方法：通过免疫组织化学（IHC）评估MMP-1、-2、-3、-9、-11、-13和-14和TIMP-1、-2、-3和-4的表达。原位杂交用于确认特定mRNA的表达。收集的临床数据包括性别、肿瘤分期、体能状态、体重减轻、血液学（血红蛋白、WBC、血小板）和生化（钠、白蛋白、碱性磷酸酶、乳酸脱氢酶）、治疗和生存。结果：评价了46例患者的样本：30例男性，16例女性：29例局限期，17例广泛期; 35例东部肿瘤协作组体能状态0-1。60%~ 70%的肿瘤细胞中MMP-1和MMP-9明显阳性，70%~ 100%的肿瘤细胞中MMP-1 α、MMP-13和MMP-14以及TIMP-2和TIMP-3明显阳性。在多变量分析中，只有肿瘤分期和TIMP-1表达减少对缓解有意义（P = 0.043），生存的重要因素是肿瘤分期（P = .0021）;体重减轻（P = .013）; MMP-3高表达的肿瘤细胞MMP-11（P = 0.031）、MMP-14（P = 0.019）、MMP和TIMP的表达在不同分期间无显著差异。结论：MMP和TIMP在SCLC中广泛表达。MMP-3、-11和-14的肿瘤表达增加是生存的独立负性预后因素。结果支持在SCLC患者中评价合成MMP抑制剂。(C)1999年，美国临床肿瘤学会。
Purpose: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are important in tumor development and progression. MMP expression has been correlated with advanced clinical stage and poor survival in some tumors, bur data for small-cell lung cancer (SCLC) are lacking. The aim ob this study was to assess the expression of MMPs and TIMPs in SCLC and to evaluate their importance relative ta standard prognostic factors,Patients and Methods: Expression of MMP-1, -2, -3, -9, -11, -13, and -14 and TIMP-1, -2, -3, and -4 was evaluated by immunohistochemistry (IHC). In situ hybridization wets used to confirm expression of specific mRNAs. Clinical data collected included sex, tumor stage, performance status, weight loss, hematology (hemoglobin, WBC, platelets) and biochemistry (sodium, albumin, alkaline phosphatase, lactate dehydrogenase), treatment, and survival,Results: Samples from 46 patients were evaluated: 30 males, 16 females: 29 limited, 17 extensive stage; 35 Eastern Cooperative Oncology Group performance status 0-1. Positive IHC staining was evident for MMP-1 and -9 in 60% to 70% of tumor cells, and for MMP-1 a, -13, and -14 and TIMP-2 and -3 in 70% to 100% of tumor cells, Stromal staining of TIMP-1 to -3 was present in less thorn 30% of specimens. On multivariate analysis, only stage and decreased tumoral expression of TIMP-1 were significant for response (P = .043), Significant factors for survival were tumor stage (P = .0021); weight loss (P = .013); and high tumor cell expression of MMP-3 (P = .077), MMP-11 (P = .031), and MMP-14 (P = .019), MMP and TIMP expression did not differ significantly between stages,Conclusion: MMPs and TIMPs are widely expressed in SCLC. Increased tumoral expression of MMP-3, -11, and -14 were independent negative prognostic factors for survival. The results support the evaluation of synthetic MMP inhibitors in patients with SCLC. (C) 1999 by American Society of Clinical Oncology.