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.
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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
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
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
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
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
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
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
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
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
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
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
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
Deryugina EI, Quigley JP (2006) Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev 25:9–34
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
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
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
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
Nagase H, Woessner JF Jr (1999) Matrix metalloproteinases. J Biol Chem 274:21491–21494
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Iizuka S, Ishimaru N, Kudo Y (2014) Matrix metalloproteinases: the gene expression signatures of head and neck cancer progression. Cancers (Basel) 6:396–415
Funding
This study was funded by the Helsinki University Hospital Research Fund (Grant number of TYH2017232) and funding from the Finska Läkaresällskapet (AM).
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An institutional research permission was granted, and the study design was approved by the Research Ethics Board of the Helsinki and Uusimaa Hospital District.
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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
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DOI: https://doi.org/10.1007/s00428-018-2365-6