Djonov Valentin, Cresto Nicola, Aebersold Daniel M, Burri Peter H, Altermatt Hans Jörg, Hristic Miriana, Berclaz Gilles, Ziemiecki Andrew, Andres Anne-Catherine
Institute of Anatomy, University of Berne, CH-3012 Berne, Switzerland.
Int J Oncol. 2002 Jul;21(1):25-30.
The metastatic potential of tumors is dependent on the ability of tumor cells to degrade extracellular matrix components by the expression of matrix metalloproteinases (MMPs) and to induce vascularisation of the tumor tissue. Thus, expression of MMPs and the number of blood vessel in tumor tissue may serve as prognostic markers of aggressive and metastasizing tumor growth. We have determined the vascularisation and the expression of MMP-2 by immuno-histochemical staining of 19 benign and 75 malignant breast tissue specimens with CD31- and MMP-2 specific antisera. The degree of vascularisation was expressed by intratumoral microvascular density (IMD), which takes into account all vessels present in a hot spot irrespective of their size. In addition, we have introduced a novel parameter, vascular grading (VG), which describes the percentage of small microvessels of <20 microm in diameter in the total number of blood vessels. IMD tended to indicate an elevated risk for metastasis formation and disease recurrence, while VG did not correlate with metastasis formation. Similarly, MMP-2 expression neither correlated with the clinical outcome of the disease nor with the classical histo-pathological parameters such as stage, grade, lymph node involvement and estrogen receptor status. Tumor cell-specific MMP-2 expression, however, showed a highly significant correlation with VG but not with IMD. These results indicate that MMP-2 expression is rather involved in the formation of small capillaries than in vessel maturation and tumor cell invasion. Thus, MMP-2 expression by tumor cells may serve as indicator of strong angiogenic induction potential of breast tumor cells.
肿瘤的转移潜能取决于肿瘤细胞通过表达基质金属蛋白酶（MMPs）降解细胞外基质成分以及诱导肿瘤组织血管生成的能力。因此，MMPs的表达和肿瘤组织中的血管数量可作为侵袭性和转移性肿瘤生长的预后标志物。我们用CD31和MMP-2特异性抗血清对19例良性和75例恶性乳腺组织标本进行免疫组织化学染色，测定了血管生成情况和MMP-2的表达。血管生成程度用瘤内微血管密度（IMD）表示，该指标考虑了热点区域内所有存在的血管，而不考虑其大小。此外，我们引入了一个新参数，血管分级（VG），它描述了直径<20微米的小微血管在血管总数中所占的百分比。IMD往往表明转移形成和疾病复发的风险升高，而VG与转移形成无关。同样，MMP-2的表达既与疾病的临床结果无关，也与经典组织病理学参数如分期、分级、淋巴结受累情况和雌激素受体状态无关。然而，肿瘤细胞特异性MMP-2表达与VG高度相关，但与IMD无关。这些结果表明，MMP-2的表达更多地参与了小毛细血管的形成，而不是血管成熟和肿瘤细胞侵袭。因此，肿瘤细胞中MMP-2的表达可能作为乳腺肿瘤细胞强大血管生成诱导潜能的指标。
