Matrix metalloproteinase (MMPs) expression has been linked to gynecological tumor aggressiveness. The objective of this study was to determine MMP-2, MMP-7, and MMP-9 and tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 expression in endometrial malignancies and their relation to clinical and histologic parameters. Formalin-fixed, paraffin-embedded tumor samples from 50 patients with endometrial carcinoma treated between 1999 and 2004 were stained with specific monoclonal antibodies. The tumors were grouped according to the FIGO classification. The staining results were compared to histologic and clinical data. Semiquantitative analysis of MMP and TIMP expression showed a significant difference in TIMP-2 expression according to the histologic subtype (P = 0.03) and also a trend towards a difference in MMP-9 expression (P = 0.05). MMP-2 expression increased and TIMP-2 expression fell as the histologic grade increased (P = 0.0007, P < 0.0001, respectively). MMP-2 expression correlated with lymph node metastasis (P = 0.04), while TIMP-2 expression correlated with the depth of myometrial invasion (P = 0.01), vasculolymphatic space involvement (P = 0.02), and lymph node metastasis (P = 0.0003). These results support the involvement of MMPs and TIMPs in endometrial tumor growth and progression. High MMP-2 and low TIMP-2 expression were the most potent markers of endometrial tumors with a high risk of local and distant spread.

译文

基质金属蛋白酶(MMPs)的表达与妇科肿瘤的侵袭性有关。这项研究的目的是确定子宫内膜恶性肿瘤中MMP-2,MMP-7和MMP-9以及金属蛋白酶组织抑制剂(TIMP)-1和TIMP-2的表达及其与临床和组织学参数的关系。用特异性单克隆抗体对1999年至2004年间接受治疗的50例子宫内膜癌患者的福尔马林固定,石蜡包埋的肿瘤样品进行染色。根据FIGO分类将肿瘤分组。将染色结果与组织学和临床数据进行比较。 MMP和TIMP表达的半定量分析显示,根据组织学亚型,TIMP-2表达存在显着差异(P = 0.03),并且MMP-9表达也呈现差异的趋势(P = 0.05)。随着组织学分级的升高,MMP-2表达增加而TIMP-2表达下降(分别为P = 0.0007,P <0.0001)。 MMP-2表达与淋巴结转移相关(P = 0.04),而TIMP-2表达与肌层浸润深度(P = 0.01),血管淋巴间隙受累(P = 0.02)和淋巴结转移(P = 0.0003)相关)。这些结果支持MMP和TIMP参与子宫内膜肿瘤的生长和进展。 MMP-2的高表达和TIMP-2的低表达是子宫内膜肿瘤最有效的标志物,具有局部和远处扩散的高风险。

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