Tumor Biology

, Volume 36, Issue 4, pp 2351–2357 | Cite as

Stoichiometric expression of MMP-2/TIMP-2 in benign and malignant tumours of the salivary gland

  • Bamidele Kolude
  • Akinyele Olumuyiwa Adisa
  • Ahmed Oluwatoyin Lawal
  • Bukola Folasade Adeyemi
  • Akindayo Olufunto Akinyamoju
Research Article


The aim of this study was to determine the expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitors of matrix metalloproteinase 2 (TIMP-2) and the MMP-2/TIMP-2 expression ratio in salivary gland tumours (SGTs). Forty-three FFPE SGTs were prepared for antibody processing to MMP-2 and TIMP-2. Two investigators utilizing Sinicrope’s method scored the uptake of immuno-stains. Cytoplasmic staining was considered as positive. Data was analysed using SPSS version 20. The significance level was set at p < 0.05. In benign SGTs, the mean score for MMP-2 was not significantly lower than that of TIMP-2 (p = 0.37). However, the mean scores for MMP-2 stain intensity and proportion were significantly higher in malignant than benign SGTs (p = 0.01 and p = 0.02 respectively). There was no significant difference in the mean MMP-2/TIMP-2 expression ratio of the malignant SGTs according to histological grade and histogenesis (p = 0.4 and p = 0.19 respectively). The MMP-2/TIMP-2 expression ratio has a higher prognostic value than the separate expressions of MMP-2 and TIMP-2.


Matrix metalloproteinase-2 Tissue inhibitor of matrix metalloproteinase-2 Salivary gland tumours 


Financial support

All the authors declare that there are no disclosures to make and that this was a self-funded study.

Conflicts of interest



  1. 1.
    Johansson N, Ahonen M, Kähäri VM. Matrix metalloproteinases in tumor invasion. Cell Mol Life Sci. 2000;57:5–15.CrossRefPubMedGoogle Scholar
  2. 2.
    Mook ORF, Frederiks WM, Van Noorden CJF. The role of gelatinases in colorectal cancer progression and metastasis. Biochem Biophys Acta. 2004;1705:69–89.PubMedGoogle Scholar
  3. 3.
    Hayakawa T, Yamashita K, Ohuchi E, Shinagawa A. Cell growth-promoting activity of tissue inhibitor of metalloproteinases-2 (TIMP-2). J Cell Sci. 1994;107:2373–9.PubMedGoogle Scholar
  4. 4.
    Stettler-Stevenson WG, Krutzsch HC, Liotta LA. TIMP-2: identification and characterization of a new member of the metalloproteinase inhibitor family. Matrix Suppl. 1992;1:299–306.Google Scholar
  5. 5.
    Gomez DE, Alonso DF, Yoshiji H, Thorgeirsson UP. Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol. 1997;74:111–22.PubMedGoogle Scholar
  6. 6.
    Zhang X, Wang Y, Tamamoto G, Tachikawa T. Expression of matrix metalloproteinases MMP-2, MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2 in the epithelium and stroma of salivary gland pleomorphic adenomas. Histopathology. 2009;55(3):250–60.CrossRefPubMedGoogle Scholar
  7. 7.
    Kayano K, Shimada T, Shinomiya T, Nakai S, Hisa Y, Aoki T, et al. Activation of pro-MMP-2 mediated by MT1-MMP in human salivary gland carcinomas: possible regulation of pro-MMP-2 activation by TIMP-2. J Pathol. 2004;202(4):403–11.CrossRefPubMedGoogle Scholar
  8. 8.
    Nagel H, Laskawi R, Wahlers A, Hemmerlein B. Expression of matrix metalloproteinases MMP-2, MMP-9 and their tissue inhibitors TIMP-1, -2, and -3 in benign and malignant tumours of the salivary gland. Histopathology. 2004;44(3):222–31.CrossRefPubMedGoogle Scholar
  9. 9.
    Batsakis JG, Luna MA. Histopathologic grading of salivary gland neoplasms: I. Mucoepidermoid carcinomas. Ann Otol Rhinol Laryngol. 1990;99:835–8.CrossRefPubMedGoogle Scholar
  10. 10.
    Seifert G, Sobin LH. The World Health Organization’s histological classification of salivary gland tumors. A commentary on the second edition. Cancer. 1992;70(2):379–85.CrossRefPubMedGoogle Scholar
  11. 11.
    Sinicrope FA, Ruan SB, Cleary KR, et al. bcl-2 and p53 onco-protein expression during colorectal tumorigenesis. Cancer Res. 1995;55:237–41.PubMedGoogle Scholar
  12. 12.
    AL-Rawi NH, Al-Samarai M, Al-Kawas S, Majeed AH. Expression of matrix metalloproteinase MMP-2 and its tissue inhibitor TIMP-2 in intraoral pleomorphic adenoma and adenoid cystic carcinoma. J Int Dent Med Res. 2011;4:1–6.Google Scholar
  13. 13.
    Matrisian L. The matrix degrading metalloproteinases. Bioassays. 1992;14:455–9.CrossRefGoogle Scholar
  14. 14.
    Kinoshita T, Sato H, Okada A, et al. TIMP-2 promotes activation of progelatinase A by membrane-type 1 matrix metalloproteinase immobilized on agarose beads. J Biol Chem. 1998;273:16098–103.CrossRefPubMedGoogle Scholar
  15. 15.
    Butler GS, Butler MJ, Atkinson SJ, et al. The TIMP-2 membrane type 1 metalloproteinase ‘receptor’ regulates the concentration and efficient activation of progelatinase A. A kinetic study. J Biol Chem. 1998;273:871–80.CrossRefPubMedGoogle Scholar
  16. 16.
    Onisto M, Riccio MP, Scannapieco P, et al. Gelatinase A/TIMP-2 imbalance in lymph-node-positive breast carcinomas, as measured by RT-PCR. Int J Cancer. 1995;63:621–6.CrossRefPubMedGoogle Scholar
  17. 17.
    Taher MG, Abdullah BH, Al-Kari LE. Expression of MMP-2 as biological markers of invasion potential in mucoepidermoid carcinoma of the oral and maxillofacial region (immunohistochemical study). Diyala J Med. 2012;3:67–72.Google Scholar
  18. 18.
    Sierl CFM, Kubben FJGM, Ganeshl S, Heerding MM, Griffioen G, Hanemaaijer R, et al. Lamers’ CBHW and Verspaget’ HW. Tissue levels of matrix metalloproteinases MMP-2 and MMP-9 are related to the overall survival of patients with gastric carcinoma. Br J Cancer. 1996;74:413–7.CrossRefGoogle Scholar
  19. 19.
    Yoshizaki T, Maruyama Y, Sato H, Furukawa M. Expression of tissue inhibitor of matrix metalloproteinase-2 correlates with activation of matrix metalloproteinase-2 and predicts poor prognosis in tongue squamous cell carcinoma. Int J Cancer. 2001;95:44–50.CrossRefPubMedGoogle Scholar
  20. 20.
    Kanayama H, Yokota K, Kurokawa Y, Murakami Y, Nishitani S, Kagawa S. Prognostic value of matrix metalloproteinase-2 expression and tissue inhibitor of metalloproteinase-2 expression in bladder cancer. Cancer. 1998;82:1359–66.CrossRefPubMedGoogle Scholar
  21. 21.
    Jinga DC, Blidaru A, Condrea I, et al. MMP-9 and MMP-2 gelatinases and TIMP-1 and TIMP-2 inhibitors in breast cancer: correlations with prognostic factors. J Cell Mol Med. 2006;10:499–510.CrossRefPubMedGoogle Scholar
  22. 22.
    Coussens LM, Fingleton B, Matrisian LM. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science. 2002;295:2387.CrossRefPubMedGoogle Scholar
  23. 23.
    Chaudhary AK, Singh M, Bharti AC, Asotra K, Sundaram S, Mehrotra R. Genetic polymorphisms of matrix metalloproteinases and their inhibitors in potentially malignant and malignant lesions of the head and neck. J Biomedical Sci. 2010;17(10):1–13.Google Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Bamidele Kolude
    • 1
  • Akinyele Olumuyiwa Adisa
    • 1
  • Ahmed Oluwatoyin Lawal
    • 1
  • Bukola Folasade Adeyemi
    • 1
  • Akindayo Olufunto Akinyamoju
    • 1
  1. 1.Department of Oral Pathology, Faculty of Dentistry, College of MedicineUniversity of IbadanIbadanNigeria

Personalised recommendations