European Archives of Oto-Rhino-Laryngology

, Volume 270, Issue 3, pp 1137–1142 | Cite as

Expression of matrix metalloproteinase-12 is correlated with extracapsular spread of tumor from nodes with metastasis in head and neck squamous cell carcinoma

  • Jin Man Kim
  • Hak Jun Kim
  • Bon Seok Koo
  • Ki Sang Rha
  • Yeo-Hoon Yoon
Head and Neck


Matrix metalloproteinases (MMPs) play an important role in tumor invasiveness and metastasis. The aim of this study was to investigate the expression pattern of MMPs in the primary tumor of head and neck squamous cell carcinomas (HNSCC) with cervical node metastasis and to correlate the expression of MMP in the primary tumor with the presence of extracapsular spread (ECS) in nodes with metastasis. A retrospective study was conducted. Paraffin blocks were obtained from 40 HNSCC patients with cervical node metastasis who underwent surgery as an initial treatment between 2004 and 2011. Expressions of MMP-2, MMP-3, MMP-12, and MMP-14 were investigated immunohistochemically. MMP-2, MMP-3, MMP-12, and MMP-14 were expressed in 27, 47.5, 55, and 57.5 % of cases, respectively. MMP-12 expression was found to be significantly associated with ECS and correlated with nodal metastasis (p = 0.024, 0.011). No relation was found between MMP expression and survival. MMP-12 expressed in the primary tumor is a molecular marker that may be useful for predicting ECS in HNSCC patients with metastatic nodal disease.


Matrix metalloproteinases Head and neck squamous cell carcinomas 


  1. 1.
    Johnson JT, Barnes EL, Myers EN et al (1981) The extracapsular spread of tumors in cervical node metastasis. Arch Otolaryngol 107:725–729PubMedCrossRefGoogle Scholar
  2. 2.
    Prim MP, De Diego JI, Hardisson D et al (1999) Extracapsular spread and desmoplastic pattern in neck lymph nodes: two prognostic factors of laryngeal cancer. Ann Otol Rhinol Laryngol 108:672–676PubMedGoogle Scholar
  3. 3.
    Myers JN, Greenberg JS, Mo V et al (2001) Extracapsular spread. A significant predictor of treatment failure in patients with squamous cell carcinoma of the tongue. Cancer 92:3030–3036PubMedCrossRefGoogle Scholar
  4. 4.
    Ferlito A, Rinaldo A, Devaney KO et al (2002) Prognostic significance of microscopic and macroscopic extracapsular spread from metastatic tumor in the cervical lymph nodes. Oral Oncol 38:747–751PubMedCrossRefGoogle Scholar
  5. 5.
    Cooper JS, Pajak TF, Forastiere AA et al (2004) Radiation Therapy Oncology Group 9501/Intergroup. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 350:1937–1944PubMedCrossRefGoogle Scholar
  6. 6.
    Bernier J, Domenge C, Ozsahin M et al (2004) European Organization for Research and Treatment of Cancer Trial 22931. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350:1945–1952PubMedCrossRefGoogle Scholar
  7. 7.
    Hanna E, Suen JY (1999) Management of the neck in squamous cell carcinoma of the head and neck. In: Myers EN, Bluestone C, Brackman D (eds) Advances in otolaryngology-head neck surgery. Mosby, St. Louis, pp 287–320Google Scholar
  8. 8.
    Werner JA, Rathcke IO, Mandic R (2002) The role of matrix metalloproteinases in squamous cell carcinomas of the head and neck. Clin Exp Metastasis 19:275–282PubMedCrossRefGoogle Scholar
  9. 9.
    Rosenthal EL, Matrisian LM (2006) Matrix metalloproteases in head and neck cancer. Head Neck 28:639–648PubMedCrossRefGoogle Scholar
  10. 10.
    Kawamata H, Uchida D, Hamano H (1998) Active-MMP2 in cancer cell nests of oral cancer patients: correlation with lymph node metastasis. Int J Oncol 13:699–704PubMedGoogle Scholar
  11. 11.
    Wiegand S, Dünne AA, Müller HH et al (2005) Meta-analysis of the significance of matrix metalloproteinases for lymph node disease in patients with head and neck squamous cell carcinoma. Cancer 104:94–100PubMedCrossRefGoogle Scholar
  12. 12.
    Katayama A, Bandoh N, Kishibe K et al (2004) Expressions of matrix metalloproteinases in early-stage oral squamous cell carcinoma as predictive indicators for tumor metastases and prognosis. Clin Cancer Res 10:634–640PubMedCrossRefGoogle Scholar
  13. 13.
    Imanishi Y, Fujii M, Tokumaru Y et al (2000) Clinical significance of expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 in human head and neck squamous cell carcinoma. Hum Pathol 31:895–904PubMedCrossRefGoogle Scholar
  14. 14.
    Ikebe T, Shinohara M, Takeuchi H (1999) Gelatinolytic activity of matrix metalloproteinase in tumor tissues correlates with the invasiveness of oral cancer. Clin Exp Metastasis 17:315–323PubMedCrossRefGoogle Scholar
  15. 15.
    Muller D, Wolf C, Abecassis J (1993) Increased stromelysin 3 gene expression is associated with increased local invasiveness in head and neck squamous cell carcinomas. Cancer Res 53:165–169PubMedGoogle Scholar
  16. 16.
    Kusukawa J, Harada H, Shima I (1996) The significance of epidermal growth factor receptor and matrix metalloproteinase-3 in squamous cell carcinoma of the oral cavity. Eur J Cancer B Oral Oncol 32:217–221CrossRefGoogle Scholar
  17. 17.
    Hofmann HS, Hansen G, Richter G et al (2005) Matrix metalloproteinase-12 expression correlates with local recurrence and metastatic disease in non-small cell lung cancer patients. Clin Cancer Res 11:1086–1092PubMedGoogle Scholar
  18. 18.
    Kerkela E, Ala-Aho R, Jeskanen L et al (2000) Expression of human macrophage metalloelastase (MMP-12) by tumor cells in skin cancer. J Invest Dermatol 114:1113–1119PubMedCrossRefGoogle Scholar
  19. 19.
    Yang X, Dong Y, Zhao J et al (2007) Increased expression of human macrophage metalloelastase (MMP-12) is associated with the invasion of endometrial adenocarcinoma. Pathol Res Pract 203:499–505PubMedCrossRefGoogle Scholar
  20. 20.
    Ding Y, Shimada Y, Gorrin-Rivas MJ et al (2002) Clinicopathological significance of human macrophage metalloelastase expression in esophageal squamous cell carcinoma. Oncology 63:378–384PubMedCrossRefGoogle Scholar
  21. 21.
    Kurahara S, Shinohara M, Ikebe T (1999) Expression of MMPS, MT-MMP, and TIMPs in squamous cell carcinoma of the oral cavity: correlations with tumor invasion and metastasis. Head Neck 21:627–638PubMedCrossRefGoogle Scholar
  22. 22.
    Okada A, Bellocq JP, Rouyer N (1995) Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas. Proc Natl Acad Sci USA 92:2730–2734PubMedCrossRefGoogle Scholar
  23. 23.
    Coatesworth AP, MacLennan K (2002) Squamous cell carcinoma of the upper aerodigestive tract: the prevalence of microscopic extracapsular spread and soft tissue deposits in the clinically N0 neck. Head Neck 24:258–261PubMedCrossRefGoogle Scholar
  24. 24.
    Puri SK, Fan CY, Hanna E (2003) Significance of extracapsular lymph node metastases in patients with head and neck squamous cell carcinoma. Curr Opin Otolaryngol Head Neck Surg 11:119–123PubMedCrossRefGoogle Scholar
  25. 25.
    Connor SE, Olliff JF (2000) Imaging of malignant cervical lymphadenopathy. Dentomaxillofac Radiol 29:133–143PubMedCrossRefGoogle Scholar
  26. 26.
    Yousem DM, Som PM, Hackney DB et al (1992) Central nodal necrosis and extracapsular neoplastic spread in cervical lymph nodes: mR imaging versus CT. Radiology 182:753–759PubMedGoogle Scholar
  27. 27.
    Cheng P, Jiang FH, Zhao LM et al (2010) Human macrophage metalloelastase correlates with angiogenesis and prognosis of gastric carcinoma. Dig Dis Sci 55:3138–3146PubMedCrossRefGoogle Scholar
  28. 28.
    Yang W, Arii S, Gorrin-Rivas MJ et al (2001) Human macrophage metalloelastase gene expression in colorectal carcinoma and its clinicopathologic significance. Cancer 91:1277–1283PubMedCrossRefGoogle Scholar
  29. 29.
    Gourin CG (2004) Is selective neck dissection adequate treatment for node-positive disease? Arch Otolaryngol Head Neck Surg 130:1431–1434PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Jin Man Kim
    • 1
  • Hak Jun Kim
    • 2
  • Bon Seok Koo
    • 2
  • Ki Sang Rha
    • 2
  • Yeo-Hoon Yoon
    • 2
  1. 1.Department of PathologyChungnam National University, School of MedicineDaejeonRepublic of Korea
  2. 2.Department of Otolaryngology, Head and Neck SurgeryChungnam National University Hospital, School of MedicineDaejeonRepublic of Korea

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