Survivin, MMP-2, MT1-MMP, and TIMP-2: their impact on survival, implantation, and proliferation of endometriotic tissues

In order to study survivin, matrix metalloproteinases (MMP-2), membranous type 1 matrix metalloproteinase (MT1-MMP), and tissue inhibitor metalloproteinase-2 (TIMP-2) expression immunohistochemically in endometriotic tissues and normal endometrium, our retrospective study considered 194 patients affected by endometriosis and 71 patients with normal endometrium. Tissue microarrays were created from paraffin-embedded blocks; immunohistochemistry was used to assess protein expression. In endometriotic tissues, survivin was expressed at a higher level than in normal endometrium; its glandular expression level was higher in non-ovarian than in ovarian endometriotic tissues and lower in stromal components. Endometrial tissues from women without endometriosis and endometriotic tissues had different matrix metalloproteinase expression profiles. MMP-2 and MT1-MMP correlated with TIMP-2 in endometriotic tissues. Furthermore, in endometriotic tissues, expression of survivin, aurora B kinase, and Ki-67 showed a significant positive correlation, which indicates a role in cellular proliferation that could be closely linked to its anti-apoptotic activity in endometriosis development. Our results imply a role for matrix metalloproteinases in endometriosis invasiveness; correlation of their expression with that of TIMP-2 underscores its possible key regulatory role.