Original Article

Virchows Archiv

, Volume 461, Issue 5, pp 589-599

First online:

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

  • Ambrogio P. LonderoAffiliated withClinic of Obstetrics and Gynecology, University of Udine
  • , Angelo CalcagnoAffiliated withClinic of Obstetrics and Gynecology, University of Udine Email author 
  • , Tiziana GrassiAffiliated withClinic of Obstetrics and Gynecology, University of Udine
  • , Stefania MarzinottoAffiliated withInstitute of Pathology, University of Udine
  • , Maria OrsariaAffiliated withInstitute of Pathology, University of Udine
  • , Carlo Alberto BeltramiAffiliated withInstitute of Pathology, University of Udine
  • , Diego MarchesoniAffiliated withClinic of Obstetrics and Gynecology, University of Udine
  • , Laura MariuzziAffiliated withInstitute of Pathology, University of Udine

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Abstract

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.

Keywords

Endometriosis Survivin Matrix metalloproteinase-2 Membranous type 1 matrix metalloproteinase Tissue inhibitor metalloproteinase-2 Tissue microarrays