Skip to main content
Log in

MMP-7 expression may influence the rate of distant recurrences and disease-specific survival in HPV-positive oropharyngeal squamous cell carcinoma

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

The objective of this study was to determine if matrix metalloproteinase-7 (MMP-7) expression is related to human papilloma virus (HPV) status, clinical parameters, and outcome in oropharyngeal squamous cell carcinoma (OPSCC). Tumor tissue specimens from 201 OPSCC patients treated with curative intent were available for immunohistochemistry, and the samples were stained with monoclonal MMP-7 antibody. All the patients were followed up at least 3 years or until death. MMP-7 expression did not differ between HPV-positive and HPV-negative patients. MMP-7 was not prognostic among patients with HPV-negative OPSCC. In the HPV-positive subgroup, patients with moderate, high, or very high MMP-7 expression had significantly worse 5-year disease-specific survival (DSS) (56.6%) than patients with absent, or low MMP-7 expression (77.2%), and MMP-7 expression appeared as a prognostic factor in the multivariate analysis. In addition, among HPV-positive OPSCC with moderate, high, or very high MMP-7 expression, the 5-year distant recurrence-free survival was significantly lower (69.6%) than in those who had low or absent MMP-7 expression (97.5%). Our results suggest that among HPV-positive OPSCC patients, high MMP-7 expression is related to worse 5-year DSS and increased rate of distant recurrences.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Shiboski CH, Schmidt BL, Jordan RC (2005) Tongue and tonsil carcinoma: increasing trends in the U.S. population ages 20-44 years. Cancer 103:1843–1849

    Article  PubMed  Google Scholar 

  2. Sturgis EM, Ang KK (2011) The epidemic of HPV-associated oropharyngeal cancer is here: is it time to change our treatment paradigms? J Natl Compr Cancer Netw 9:665–673

    Article  Google Scholar 

  3. Chaturvedi AK, Anderson WF, Lortet-Tieulent J, Curado MP, Ferlay J, Franceschi S, Rosenberg PS, Bray F, Gillison ML (2013) Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol 31:4550–4559

    Article  PubMed  PubMed Central  Google Scholar 

  4. Ragin CC, Taioli E (2007) Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: review and meta-analysis. Int J Cancer 121:1813–1820

    Article  PubMed  CAS  Google Scholar 

  5. Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, Jiang B, Goodman MT, Sibug-Saber M, Cozen W, Liu L, Lynch CF, Wentzensen N, Jordan RC, Altekruse S, Anderson WF, Rosenberg PS, Gillison ML (2011) Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 29:4294–4301

    Article  PubMed  PubMed Central  Google Scholar 

  6. Nasman A, Attner P, Hammarstedt L, Du J, Eriksson M, Giraud G, Ahrlund-Richter S, Marklund L, Romanitan M, Lindquist D, Ramqvist T, Lindholm J, Sparen P, Ye W, Dahlstrand H, Munck-Wikland E, Dalianis T (2009) Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma? Int J Cancer 125:362–366

    Article  PubMed  CAS  Google Scholar 

  7. Rietbergen MM, Leemans CR, Bloemena E, Heideman DA, Braakhuis BJ, Hesselink AT, Witte BI, Baatenburg de Jong RJ, Meijer CJ, Snijders PJ, Brakenhoff RH (2013) Increasing prevalence rates of HPV attributable oropharyngeal squamous cell carcinomas in the Netherlands as assessed by a validated test algorithm. Int J Cancer 132:1565–1571

    Article  PubMed  CAS  Google Scholar 

  8. Nichols AC, Palma DA, Dhaliwal SS, Tan S, Theuer J, Chow W, Rajakumar C, Um S, Mundi N, Berk S, Zhou R, Basmaji J, Rizzo G, Franklin JH, Fung K, Kwan K, Wehrli B, Salvadori MI, Winquist E, Ernst S, Kuruvilla S, Read N, Venkatesan V, Todorovic B, Hammond JA, Koropatnick J, Mymryk JS, Yoo J, Barrett JW (2013) The epidemic of human papillomavirus and oropharyngeal cancer in a Canadian population. Curr Oncol 20:212–219

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, Zahurak ML, Daniel RW, Viglione M, Symer DE, Shah KV, Sidransky D (2000) Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92:709–720

    Article  PubMed  CAS  Google Scholar 

  10. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363:24–35

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Hua H, Li M, Luo T, Yin Y, Jiang Y (2011) Matrix metalloproteinases in tumorigenesis: an evolving paradigm. Cell Mol Life Sci 68:3853–3868

    Article  PubMed  CAS  Google Scholar 

  12. Sorsa T, Tjaderhane L, Konttinen YT, Lauhio A, Salo T, Lee HM, Golub LM, Brown DL, Mantyla P (2006) Matrix metalloproteinases: contribution to pathogenesis, diagnosis and treatment of periodontal inflammation. Ann Med 38:306–321

    Article  PubMed  CAS  Google Scholar 

  13. Deryugina EI, Quigley JP (2006) Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev 25:9–34

    Article  PubMed  CAS  Google Scholar 

  14. Herfs M, Yamamoto Y, Laury A, Wang X, Nucci MR, McLaughlin-Drubin ME, Munger K, Feldman S, McKeon FD, Xian W, Crum CP (2012) A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer. Proc Natl Acad Sci U S A 109:10516–10521

    Article  PubMed  PubMed Central  Google Scholar 

  15. Morbini P, Capello GL, Alberizzi P, Benazzo M, Paglino C, Comoli P, Pedrazzoli P (2015) Markers of squamocolumnar junction cells in normal tonsils and oropharyngeal cancer with and without HPV infection. Histol Histopathol 30:833–839

    PubMed  CAS  Google Scholar 

  16. Yamamoto H, Itoh F, Iku S, Adachi Y, Fukushima H, Sasaki S, Mukaiya M, Hirata K, Imai K (2001) Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human pancreatic adenocarcinomas: clinicopathologic and prognostic significance of matrilysin expression. J Clin Oncol 19:1118–1127

    Article  PubMed  CAS  Google Scholar 

  17. Wang WS, Chen PM, Wang HS, Liang WY, Su Y (2006) Matrix metalloproteinase-7 increases resistance to Fas-mediated apoptosis and is a poor prognostic factor of patients with colorectal carcinoma. Carcinogenesis 27:1113–1120

    Article  PubMed  CAS  Google Scholar 

  18. Nagase H, Woessner JF Jr (1999) Matrix metalloproteinases. J Biol Chem 274:21491–21494

    Article  PubMed  CAS  Google Scholar 

  19. Ii M, Yamamoto H, Adachi Y, Maruyama Y, Shinomura Y (2006) Role of matrix metalloproteinase-7 (matrilysin) in human cancer invasion, apoptosis, growth, and angiogenesis. Exp Biol Med (Maywood) 231:20–27

    Article  CAS  Google Scholar 

  20. Chuang HC, Su CY, Huang HY, Huang CC, Chien CY, Du YY, Chuang JH (2008) Active matrix metalloproteinase-7 is associated with invasion in buccal squamous cell carcinoma. Mod Pathol 21:1444–1450

    Article  PubMed  CAS  Google Scholar 

  21. de Vicente JC, Lequerica-Fernandez P, Santamaria J, Fresno MF (2007) Expression of MMP-7 and MT1-MMP in oral squamous cell carcinoma as predictive indicator for tumor invasion and prognosis. J Oral Pathol Med 36:415–424

    Article  PubMed  CAS  Google Scholar 

  22. Masaki T, Matsuoka H, Sugiyama M, Abe N, Goto A, Sakamoto A, Atomi Y (2001) Matrilysin (MMP-7) as a significant determinant of malignant potential of early invasive colorectal carcinomas. Br J Cancer 84:1317–1321

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Ramankulov A, Lein M, Johannsen M, Schrader M, Miller K, Jung K (2008) Plasma matrix metalloproteinase-7 as a metastatic marker and survival predictor in patients with renal cell carcinomas. Cancer Sci 99:1188–1194

    Article  PubMed  CAS  Google Scholar 

  24. Weber A, Hengge UR, Stricker I, Tischoff I, Markwart A, Anhalt K, Dietz A, Wittekind C, Tannapfel A (2007) Protein microarrays for the detection of biomarkers in head and neck squamous cell carcinomas. Hum Pathol 38:228–238

    Article  PubMed  CAS  Google Scholar 

  25. Makinen LK, Hayry V, Hagstrom J, Sorsa T, Passador-Santos F, Keski-Santti H, Haukka J, Makitie AA, Haglund C, Atula T (2014) Matrix metalloproteinase-7 and matrix metalloproteinase-25 in oral tongue squamous cell carcinoma. Head Neck 36:1783–1788

    Article  PubMed  Google Scholar 

  26. Jouhi L, Mohamed H, Makitie A, Remes SM, Haglund C, Atula T, Hagstrom J (2017) Toll-like receptor 5 and 7 expression may impact prognosis of HPV-positive oropharyngeal squamous cell carcinoma patients. Cancer Immunol Immunother 66:1619–1629

    Article  PubMed  CAS  Google Scholar 

  27. Mirghani H, Amen F, Blanchard P, Moreau F, Guigay J, Hartl DM, Lacau St Guily J (2015) Treatment de-escalation in HPV-positive oropharyngeal carcinoma: ongoing trials, critical issues and perspectives. Int J Cancer 136:1494–1503

    Article  PubMed  CAS  Google Scholar 

  28. Fung N, Faraji F, Kang H, Fakhry C (2017) The role of human papillomavirus on the prognosis and treatment of oropharyngeal carcinoma. Cancer Metastasis Rev 36:449–461

    Article  PubMed  Google Scholar 

  29. Reimers N, Kasper HU, Weissenborn SJ, Stutzer H, Preuss SF, Hoffmann TK, Speel EJ, Dienes HP, Pfister HJ, Guntinas-Lichius O, Klussmann JP (2007) Combined analysis of HPV-DNA, p16 and EGFR expression to predict prognosis in oropharyngeal cancer. Int J Cancer 120:1731–1738

    Article  PubMed  CAS  Google Scholar 

  30. Lee SY, Park SY, Kim SH, Choi EC (2011) Expression of matrix metalloproteinases and their inhibitors in squamous cell carcinoma of the tonsil and their clinical significance. Clin Exp Otorhinolaryngol 4:88–94

  31. Chaturvedi AK, Engels EA, Anderson WF, Gillison ML (2008) Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. J Clin Oncol 26:612–619

    Article  PubMed  Google Scholar 

  32. Gillison ML, D'Souza G, Westra W, Sugar E, Xiao W, Begum S, Viscidi R (2008) Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst 100:407–420

    Article  PubMed  Google Scholar 

  33. Rietbergen MM, Braakhuis BJ, Moukhtari N, Bloemena E, Brink A, Sie D, Ylstra B, Baatenburg de Jong RJ, Snijders PJ, Brakenhoff RH, Leemans CR (2014) No evidence for active human papillomavirus (HPV) in fields surrounding HPV-positive oropharyngeal tumors. J Oral Pathol Med 43:137–142

    Article  PubMed  CAS  Google Scholar 

  34. O'Sullivan B, Huang SH, Siu LL, Waldron J, Zhao H, Perez-Ordonez B, Weinreb I, Kim J, Ringash J, Bayley A, Dawson LA, Hope A, Cho J, Irish J, Gilbert R, Gullane P, Hui A, Liu FF, Chen E, Xu W (2013) Deintensification candidate subgroups in human papillomavirus-related oropharyngeal cancer according to minimal risk of distant metastasis. J Clin Oncol 31:543–550

    Article  PubMed  CAS  Google Scholar 

  35. Dunne AA, Grobe A, Sesterhenn AM, Barth P, Dalchow C, Werner JA (2005) Influence of matrix metalloproteinase 9 (MMP-9) on the metastatic behavior of oropharyngeal cancer. Anticancer Res 25:4129–4134

    PubMed  CAS  Google Scholar 

  36. Burduk PK, Bodnar M, Sawicki P, Szylberg L, Wisniewska E, Kazmierczak W, Martynska M, Marszalek A (2015) Expression of metalloproteinases 2 and 9 and tissue inhibitors 1 and 2 as predictors of lymph node metastases in oropharyngeal squamous cell carcinoma. Head Neck 37:418–422

    Article  PubMed  Google Scholar 

  37. Iizuka S, Ishimaru N, Kudo Y (2014) Matrix metalloproteinases: the gene expression signatures of head and neck cancer progression. Cancers (Basel) 6:396–415

    Article  CAS  Google Scholar 

Download references

Funding

This study was funded by the Helsinki University Hospital Research Fund (Grant number of TYH2017232) and funding from the Finska Läkaresällskapet (AM).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Seija I. Vento.

Ethics declarations

An institutional research permission was granted, and the study design was approved by the Research Ethics Board of the Helsinki and Uusimaa Hospital District.

Conflict of interest

None declared.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vento, S.I., Jouhi, L., Mohamed, H. et al. MMP-7 expression may influence the rate of distant recurrences and disease-specific survival in HPV-positive oropharyngeal squamous cell carcinoma. Virchows Arch 472, 975–981 (2018). https://doi.org/10.1007/s00428-018-2365-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-018-2365-6

Keywords

Navigation