Garzetti G G, Ciavattini A, Lucarini G, Goteri G, Romanini C, Biagini G
Institute of Obstetrics and Gynecology, University of Ancona, Italy.
Anticancer Res. 1996 Jul-Aug;16(4A):2123-7.
72 KDa metalloproteinase (MMP-2) is an enzyme present in neoplastic cells and also in normal fibroblasts. It specifically cleaves type IV collagen, and therefore may play a critical role in tumor invasion and metastasis mechanisms. The aim of the present study was to determine serum levels of MMP-2 in serous ovarian tumors, and compare these with serum levels of CA 125. Ten primary ovarian serous cystadenocarcinomas, 5 borderline tumors, and 10 serous cystadenomas, all treated with primary surgery, were recruited from our series of serous ovarian tumors, and studied. Patients' serum samples were obtained before surgery, and the MMP-2 levels were measured by the substrate capture enzyme-linked immunosorbet assay. The analysis of serum MMP-2, gave values significantly higher in cystadenocarcinomas than in borderline tumors and cystadenomas (one way analysis of variance, P < 0.001); in particular, serum MMP-2 was significantly correlated to the MMP-2 immunostaining of the tumor (Spearman correlation, r = 0.82, and P < 0.001). An arbitrary cutoff of the median value of normal adult female samples (0.22 units) was chosen, and all except for one patient with cystadenocarcinoma was shown to have serum MMP-2 levels above the cutoff value, with 90% sensitivity, 70% specificity, and a 75% positive predictive value (50% of Cohen's Kappa); on the other hand, CA 125 showed 80% sensitivity, and a 73% positive predictive value. The association of serum MMP-2 with CA 125 increased sensitivity to 100% in patients with cystadenocarcinoma, with 70% persisting specificity and a 77% positive predictive value (54% of Cohen's Kappa). Serum MMP-2 levels were found to be significantly increased in patients with cystadenocarcinoma in comparison with borderline tumors and cystadenomas, showing a direct relationship with tissutal MMP-2 expression in serous ovarian tumors. Although our results were preliminary, they clearly suggested that serum MMP-2 may be an interesting diagnostic marker for cystadenocarcinomas.
72千道尔顿金属蛋白酶(MMP - 2)是一种存在于肿瘤细胞以及正常成纤维细胞中的酶。它能特异性地裂解IV型胶原蛋白,因此可能在肿瘤侵袭和转移机制中发挥关键作用。本研究的目的是测定浆液性卵巢肿瘤患者血清中MMP - 2的水平,并将其与CA 125的血清水平进行比较。从我们的浆液性卵巢肿瘤系列中选取了10例原发性卵巢浆液性囊腺癌、5例交界性肿瘤和10例浆液性囊腺瘤患者,所有患者均接受了初次手术并进行研究。在手术前采集患者的血清样本,采用底物捕获酶联免疫吸附测定法测量MMP - 2水平。血清MMP - 2分析结果显示,囊腺癌患者的MMP - 2值显著高于交界性肿瘤和囊腺瘤患者(单因素方差分析,P < 0.001);特别是,血清MMP - 2与肿瘤的MMP - 2免疫染色显著相关(Spearman相关性分析,r = 0.82,P < 0.001)。选择正常成年女性样本中位数(0.22单位)作为任意截断值,除1例囊腺癌患者外,所有患者血清MMP - 2水平均高于截断值,其敏感性为90%,特异性为70%,阳性预测值为75%(Cohen's Kappa值的50%);另一方面,CA 125的敏感性为80%,阳性预测值为73%。血清MMP - 2与CA 125联合检测时,囊腺癌患者的敏感性提高到100%,特异性保持在70%,阳性预测值为77%(Cohen's Kappa值的54%)。与交界性肿瘤和囊腺瘤患者相比,囊腺癌患者血清MMP - 2水平显著升高,表明其与浆液性卵巢肿瘤组织中的MMP - 2表达呈直接关系。虽然我们的结果是初步的,但它们清楚地表明血清MMP - 2可能是囊腺癌一个有价值的诊断标志物。