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Expression of matrix metalloproteinases (MMPs-2, -7, -9, and -26) and tissue inhibitors of metalloproteinases (TIMPs-1 and -2) in pleomorphic adenomas and adenoid cystic carcinomas

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Abstract

Purpose

To compare the immunohistochemical expression of matrix metalloproteinases-2, -7, -9 and -26 and tissue inhibitors of metalloproteinases-1 and -2 in pleomorphic adenomas and adenoid cystic carcinomas of the minor salivary glands.

Methods

Twenty cases of pleomorphic adenomas and 20 cases of adenoid cystic carcinomas were evaluated for the immunohistochemical expression of matrix metalloproteinases-2, -7, -9, and -26 and tissue inhibitors-1 and -2 in tumor parenchyma.

Results

Most pleomorphic adenomas and adenoid cystic carcinomas showed high expression of matrix metalloproteinases and tissue inhibitors, predominantly located in the tumor cells. There was no statistically significant difference in the expression of the metalloproteinases-2 (p = 0.359), -7 (p = 0.081), and -26 (p = 0 553), as well as the tissue inhibitors-1 (p = 0.657), and -2 (p = 0.248) between the parenchyma of the studied tumors. Only matrix metalloproteinase-9 showed a significant difference in expression between the two tumors, with adenoid cystic carcinoma showing a more intense staining for this gelatinase (p = 0.041).

Conclusions

The expression of the studied metalloproteinases suggests the involvement of these enzymes in the tissue remodeling process in pleomorphic adenomas and adenoid cystic carcinomas, but only MMP-9, significantly expressed in the adenoid cystic carcinomas, appears to be involved in the process of invasiveness and more aggressive behavior of these tumors. Additionally, results point that TIMPs-1 and -2 may have more complex functions besides metalloproteinase inhibition, which may be related to the pathogenesis and biological behavior of salivary gland tumors.

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References

  1. Barnes L, Eveson JW, Reichart P, Sidransky D (2005) World health organization classification of tumors: pathology & genetics—head and neck tumors, 3 edn. IARC Press, Lyon

    Google Scholar 

  2. Sung MW, Kim KH, Kim JW et al (2003) Clinicopathologic predictors and impact of distant metastasis from adenoid cystic carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 129(11):1193–1197. https://doi.org/10.1001/archotol.129.11.1193.

    Article  PubMed  Google Scholar 

  3. El-Naggar AK et al (2017) WHO classification of head and neck tumors, 4 edn. IARC Press, Lyon

    Google Scholar 

  4. Bobbio A, Copelli C, Ampollini L et al (2008) Lung metastasis resection of adenoid cystic carcinoma of salivary glands. Eur J Cardiothorac Surg 33(5):790–793. https://doi.org/10.1016/j.ejcts.2007.12.057

    Article  PubMed  Google Scholar 

  5. Nagase H, Visse R, Murphy G (2006) Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res 69(3):562–573. https://doi.org/10.1016/j.cardiores.2005.12.002

    Article  CAS  PubMed  Google Scholar 

  6. Barros SSLV, Henriques ÁCG, Pereira KMA et al (2011) Immunohistochemical expression of matrix metalloproteinases in squamous cell carcinoma of the tongue and lower lip. Arch Oral Biol 56(8):752–760. https://doi.org/10.1016/j.archoralbio.2010.11.022

    Article  CAS  PubMed  Google Scholar 

  7. Souza Freitas V, de Andrade Santos PP, Almeida Freitas RD et al (2011) Mast cells and matrix metalloproteinase 9 expression in actinic cheilitis and lip squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 112(3):342–348. https://doi.org/10.1016/j.tripleo.2011.02.032.

    Article  PubMed  Google Scholar 

  8. Kayano K, Shimada T, Shinomiya T et al (2004) 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 202(4):403–411. https://doi.org/10.1002/path.1541

    Article  CAS  PubMed  Google Scholar 

  9. Wang Y, Irie T, Aida T, Tachikawa T (2005) Expression of TIMP-1 and -2 in different growth patterns of adenoid cystic carcinoma. Oral Oncol 41(8):821–827. https://doi.org/10.1016/j.oraloncology.2005.04.009

    Article  CAS  PubMed  Google Scholar 

  10. Nagel H, Laskawi R, Wahlers A, Hemmerlein B (2004) 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 44(3):222–231

    Article  CAS  Google Scholar 

  11. Hu JA, Xu JY, Li YN et al (2005) Expression of MMP-2 and E-CD in salivary mucoepidermoid carcinoma and its correlation with infiltration, metastasis and prognosis. Zhejiang Da Xue Xue Bao Yi Xue Ban 34(5):421–426

    CAS  PubMed  Google Scholar 

  12. Chen Y, Tian K, Geng N et al (2005) The expression of matrix metalloproteinases and their tissue inhibitors in pleomorphic adenoma]. Zhonghua Kou Qiang Yi Xue Za Zhi 40(1):58–61

    CAS  PubMed  Google Scholar 

  13. Lipari L, Mauro A, Gallina S, Tortorici S, Buscemi M, Tete S, Gerbino A (2012) Expression of gelatinases (Mmp-2, Mmp-9) and cyclooxygenases (Cox1, Cox-2) in some benign salivary gland tumors. Int J Immunopathol Pharmacol 25(1):107–115. https://doi.org/10.1177/039463201202500113

    Article  CAS  PubMed  Google Scholar 

  14. Mardani M, Andisheh-Tadbir A, Khademi B et al (2014) Serum level of matrix metalloproteinase-9 in patients with salivary gland tumor. J Dent Shiraz Univ Med Sci 15(4):199–203

    Google Scholar 

  15. Tang YL, Liu X, Gao SY et al (2015) WIP1 stimulates migration and invasion of salivary adenoid cystic carcinoma by inducing MMP-9 and VEGF-C. Oncotarget 6(11):9031–9044. https://doi.org/10.18632/oncotarget.3320

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kolude B, Akinyele A, Ahmed L et al (2015) Stoichiometric expression of MMP-2/TIMP-2 in benign and malignant tumours of the salivary gland. Tumor Biol 36:2351–2357. https://doi.org/10.1007/s13277-014-2842-8

    Article  CAS  Google Scholar 

  17. Zhao L, Jiang L, Du P et al (2016) Expression of SKA1 and MMP-9 in primary salivary adenoid cystic carcinoma: Correlation with tumor progression and patient prognosis. Acta Otolaryngol 136(6):575–579. https://doi.org/10.3109/00016489.2016.1142117

    Article  CAS  PubMed  Google Scholar 

  18. Luukkaa H, Klemi P, Hirsimaki P et al (2010) Matrix metalloproteinase (MMP)-7 in salivary gland cancer. Acta Oncol 49(1):85–90. https://doi.org/10.3109/02841860903287197 (a)

    Article  CAS  PubMed  Google Scholar 

  19. Daa T, Kashima K, Kondo Y et al (2008) Aberrant methylation in promoter regions of cyclin-dependent kinase inhibitor genes in adenoid cystic carcinoma of the salivary gland. APMIS 116(1):21–26. https://doi.org/10.1111/j.1600-0463.2008.00773.x

    Article  CAS  PubMed  Google Scholar 

  20. Polette M, Nawrocki-Raby B, Gilles C et al (2004) Tumour invasion and matrix metalloproteinases. Crit Rev Oncol Hematol 49(3):179–186. https://doi.org/10.1016/j.critrevonc.2003.10.008

    Article  PubMed  Google Scholar 

  21. Li M, Yamamoto H, Adachi Y et al (2006) Role of matrix metalloproteinase-7 (matrilysin) in human cancer invasion, apoptosis, growth, and angiogenesis. Exp Biol Med (Maywood) 231(1):20–27

    Article  Google Scholar 

  22. Zhang CY, Mao L, Li L et al (2007) Promoter methylation as a common mechanism for inactivating E-cadherin in human salivary gland adenoid cystic carcinoma. Cancer 110(1):87–95. https://doi.org/10.1002/cncr.22758

    Article  PubMed  Google Scholar 

  23. Wang R, Geng N, Zhou Y et al (2015) Aberrant Wnt-1/beta-catenin signaling and WIF-1 deficiency are important events which promote tumor cell invasion and metastasis in salivary gland adenoid cystic carcinoma. Bio-Med Mater Eng 26(1): S2145-153. https://doi.org/10.3233/BME-151520

    Article  CAS  Google Scholar 

  24. Bourboulia D, Stetler-Stevenson WG (2010) Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): positive and negative regulators in tumor cell adhesion. Semin Cancer Biol 20(3):161–168. https://doi.org/10.1016/j.semcancer.2010.05.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Tian K, Chen Y, Geng N et al (2005) Relationship of the disturbed balance between matrix metalloproteinases and their tissue inhibitors and the invasion of malignant salivary gland tumours. Hua xi kou qiang yi xue za zhi 23(4):273–276

    CAS  PubMed  Google Scholar 

  26. Luukkaa H, Klemi P, Leivo I et al (2010) Expression of matrix metalloproteinase-1, -7, -9, -13, Ki-67, and HER-2 in epithelial-myoepithelial salivary gland cancer. Head Neck 32(8):1019–1027. https://doi.org/10.1002/hed.21277(b)

    Article  PubMed  Google Scholar 

  27. Verma RP, Hansch C (2007) Matrix metalloproteinases (MMPs): chemical-biological functions and (Q)SARs. Bioorg Med Chem 15(6):2223–2268. https://doi.org/10.1016/j.bmc.2007.01.011

    Article  CAS  PubMed  Google Scholar 

  28. Monaghan H, MacWhinnie N, Williams AR (2007) The role of matrix metalloproteinases-2, -7 and -9 and beta-catenin in high grade endometrial carcinoma. Histopathology 50(3):348–357. https://doi.org/10.1111/j.1365-2559.2007.02612.x

    Article  CAS  PubMed  Google Scholar 

  29. Kerkela E, Saarialho-Kere U (2003) Matrix metalloproteinases in tumor progression: focus on basal and squamous cell skin cancer. Exp Dermatol 12(2):109–125

    Article  CAS  Google Scholar 

  30. Kuula H, Salo T, Pirila E et al (2008) Human beta-defensin-1 and -2 and matrix metalloproteinase-25 and -26 expression in chronic and aggressive periodontitis and in peri-implantitis. Arch Oral Biol 53(2):175–186. https://doi.org/10.1016/j.archoralbio.2007.09.010

    Article  CAS  PubMed  Google Scholar 

  31. Uria JA, Lopez-Otin C (2000) Matrilysin-2, a new matrix metalloproteinase expressed in human tumors and showing the minimal domain organization required for secretion, latency, and activity. Cancer Res 60(17):4745–4751

    CAS  PubMed  Google Scholar 

  32. Luukkaa H, Klemi P, Hirsimaki P et al (2008) Matrix metalloproteinase (MMP)-1, -9 and -13 as prognostic factors in salivary gland cancer. Acta Otolaryngol 128(4):482–490. https://doi.org/10.1080/00016480801922895

    Article  CAS  PubMed  Google Scholar 

  33. Zhang X, Wang Y, Yamamoto G, Tachikawa T (2009) 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 55(3):250–260. https://doi.org/10.1111/j.1365-2559.2009.03355.x

    Article  PubMed  Google Scholar 

  34. Raitz R, Martins MD, Araujo VC (2003) A study of the extracellular matrix in salivary gland tumors. J Oral Pathol Med 32(5):290–296

    Article  CAS  Google Scholar 

  35. Bento PM, Freitas RA, Pinto LP, Souza LB (2006) Tenascin and fibronectin in pleomorphic adenoma of the salivary gland. J Appl Oral Sci 14(3):198–202

    Article  Google Scholar 

  36. de Vicente JC, Lequerica-Fernandez P, Lopez-Arranz JS et al (2008) Expression of matrix metalloproteinase-9 in high-grade salivary gland carcinomas is associated with their metastatic potential. Laryngoscope 118(2):247–251. https://doi.org/10.1097/MLG.0b013e318158f754

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

Supported by CNPq-Conselho Nacional de Desenvolvimento Científico e Tecnológico (Grant no. 307539/2010-5). Jean Nunes dos Santos, Cassiano Francisco Weege Nonaka, Leão Pereira Pinto and Lelia Batista de Souza are research fellows at CNPq, Brazil.

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Correspondence to Lélia Batista de Souza.

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None of the authors has any conflict of interest, financial or otherwise.

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This study was approved by the UFRN Research Ethics Committee, Natal, Brazil (No. 203/2008).

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Certify that all authors (Valéria Souza Freitas; Jean Nunes dos Santos; Pedro Paulo de Andrade Santos; Cassiano Francisco Weege Nonaka; Leão Pereira Pinto and Lélia Batista de Souza) have viewed and agreed to the manuscript submitted.

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Souza Freitas, V., dos Santos, J.N., de Andrade Santos, P.P. et al. Expression of matrix metalloproteinases (MMPs-2, -7, -9, and -26) and tissue inhibitors of metalloproteinases (TIMPs-1 and -2) in pleomorphic adenomas and adenoid cystic carcinomas. Eur Arch Otorhinolaryngol 275, 3075–3082 (2018). https://doi.org/10.1007/s00405-018-5176-0

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