Matrix metalloproteinases in carcinoma of unknown primary

Matrix metalloproteinases in carcinoma of unknown primary
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DOI:
10.1002/cncr.21454
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发表时间:
2005-11-15
期刊:
影响因子:
6.2
通讯作者:
Pavlidis, N
Pavlidis, N
中科院分区:
医学1区
文献类型:
--
作者:
Karavasilis, V;Malamou-Mitsi, V;Pavlidis, N

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背景目的:研究原发性不明癌(CUP)中蛋白水解相关分子基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)及金属蛋白酶组织抑制剂-1(TIMP-1)的表达。使用了来自75名诊断为CUP的患者的石蜡包埋的肿瘤材料。肿瘤组织学类型为腺癌(77%)、未分化癌(19%)和鳞状细胞癌(4%),患者分为有利(62%)和不利(38%)亚组。MMP-2、MMP-9和TIMP-1的组织表达通过使用特异性单克隆抗体进行评估,并通过视觉染色评分进行评价。研究分子的表达进行了分析,对临床病理数据。MMP-2在69%(强表达49%)、MMP-9在49%(强表达36%)、TIMP-1在79%(强表达44%)的研究病例中被发现表达。MMP-2和MMP-9的表达呈正相关。与良性肿瘤相比,不良肿瘤中TIMP-1显著更高,并且与患者的生存期更短相关(7.5 vs. 12个月)。未发现其他相关性。MMP-2、MMP-9和TIMP-1在CUP中广泛表达,提示蛋白水解在这些肿瘤中起重要作用。TIMP-1可能是CUP患者预后不良的一个标志物。
BACKGROUND. The purpose was to study proteolysis-related molecules, matrix metalloproteinase-2 (MMP-2) and MMP-9 and tissue inhibitor of metalloproteinases-1 (TIMP-1), in carcinoma of unknown primary (CUP).METHODS. Paraffin-embedded tumor material from 75 patients diagnosed with CUP was used. Tumor histologies were adenocarcinoma (77%), undifferentiated carcinoma (19%), and squamous cell carcinoma (4%) and patients were categorized into favorable (62%) and unfavorable (38%) subsets. The tissue expression of MMP-2, MMP-9, and TIMP-1 was assessed by use of specific monoclonal antibodies and evaluated by means of a visual staining score. The expression of molecules studied was analyzed against clinicopathological data.RESULTS. MMP-2 was found expressed in 69% (strong expression in 49%), MMP-9 in 49% (strong in 36%), and TIMP-1 in 79% (strong in 44%) of studied cases. The expression of MMP-2 correlated positively with MMP-9. TIMP-1 was significantly higher in unfavorable compared with favorable tumors and was associated with a shorter survival of patients (7.5 vs. 12 mos). No other associations were detected.CONCLUSIONS. MMP-2, MMP-9, and TIMP-1 are widely expressed in CUP, suggesting an essential role of proteolysis in these tumors. TIMP-1 may be considered a possible marker of poor prognosis in CUP patients.