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

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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.

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Abbreviations

ABK:

Aurora B kinase

APC:

Adenomatous polyposis coli

ASRM:

American Society of Reproductive Medicine

ET:

Endometriotic tissue

IAP:

Inhibitor of apoptosis protein

IQR:

Interquartile range

MMP-2:

Matrix metalloproteinase-2

MMP:

Matrix metalloproteinase

MT1-MMP:

Membranous type 1 matrix metalloproteinase

PR:

Progesterone receptor

TIMP-2:

Tissue inhibitor metalloproteinase-2

TMA:

Tissue microarray

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Acknowledgments

We are grateful to Dr. Enrica Stella for her help in this study, Matteo De Luca for the technical assistance in realizing TMA, and to Dr. Serena Bertozzi for her help in preparation of this manuscript. Dr. Giorgio Zaccagna, Dr. Guido Borgna and Dr. Marco Pittino are thanked for their helpful collaboration. This study was financially supported by the University of Udine.

Conflict of interest

The authors declare that they have no potential conflicts of interest relevant to this article.

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Authors and Affiliations

  1. Clinic of Obstetrics and Gynecology, University of Udine, Piazzale SM della Misericordia, 15-33100, Udine, Italy

    Ambrogio P. Londero, Angelo Calcagno, Tiziana Grassi & Diego Marchesoni

  2. Institute of Pathology, University of Udine, 33100, Udine, Italy

    Stefania Marzinotto, Maria Orsaria, Carlo Alberto Beltrami & Laura Mariuzzi

Authors
  1. Ambrogio P. Londero
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  2. Angelo Calcagno
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  3. Tiziana Grassi
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  4. Stefania Marzinotto
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  5. Maria Orsaria
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  6. Carlo Alberto Beltrami
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  7. Diego Marchesoni
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  8. Laura Mariuzzi
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Corresponding author

Correspondence to Angelo Calcagno.

Additional information

Ambrogio P. Londero and Angelo Calcagno equally contributed to this work.

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Londero, A.P., Calcagno, A., Grassi, T. et al. Survivin, MMP-2, MT1-MMP, and TIMP-2: their impact on survival, implantation, and proliferation of endometriotic tissues. Virchows Arch 461, 589–599 (2012). https://doi.org/10.1007/s00428-012-1301-4

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  • DOI: https://doi.org/10.1007/s00428-012-1301-4

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