Expression of TIMP-2 in HPV-16 infected oral squamous cell carcinoma in patients in Iraq
Keywords:TIMP-2. HPV. Iraq. Oral cancer.
Aim: To determine the expression of tissue inhibitors of metalloproteinases (TIMP-2) in oral squamous cell carcinoma (OSCC) and the difference in its expression level between positive and negative HPV-16 (human papilloma virus- 16) OSCC patients. Methods: This study was conducted on 33 biopsies obtained from patients with OSCC and 10 normal oral mucosa as controls. In situ hybridization (ISH) was used to investigate the presence of HPV-16, while immunohistochemistry (IHC) was used to estimate the expression level of TIMP-2. Results: The TIMP-2 was expressed in 27 (81.8%) of OSCC sections with no significant difference between its expression level in HPV-16 positive and HPV-16 negative OSCC cases (p=0.058). TIMP-2 was found to be highly expressed in OSCC sections, and the presence of HPV was not related to its overexpression. Conclusions: The percentage of samples that appeared to accommodate detectable HPV-16 was high, but no significant difference was observed in relation to TIMP-2 expression level. Future studies with a larger number of patients are highly recommended to address the possible association between TIMp-2 and OSCC positive HPV-16.
Wang B, Zhang S, Yue K, Wang XD. The recurrence and survival of oral squamous cell carcinoma: a report of 275 cases. Chin J Cancer. 2013 Nov;32(11):614-8. doi: 10.5732/cjc.012.10219.
Scully C, Kirby J. Statement on mouth cancer diagnosis and prevention. Br Dent J. 2014 Jan;216(1):37-8. doi: 10.1038/sj.bdj.2013.1235
Sasahira T, Kurihara M, Nishiguchi Y, Fujiwara R, Kirita T, Kuniyasu H. NEDD 4 binding protein 2-like 1 promotes cancer cell invasion in oral squamous cell carcinoma. Virchows Archiv. 2016 Aug;469(2):163-72. doi: 10.1007/s00428-016-1955-4.
Oral Cancer Foundation. Oral Cancer Facts. The Oral Cancer Foundation. Available from: http://www.oralcancerfoundation.org/facts.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. doi: 10.3322/caac.20107
Lima MAP, Silva CGL, Rabenhorst SHB. Association between human papillomavirus (HPV) and the oral squamous cell carcinoma: a systematic review. J Bras Patol Med Lab. 2014 Feb [cited 2014 Apr];50(1):75-84. Available from: http://www.scielo.br/pdf/jbpml/v50n1/1676-2444-jbpml-50-01-0075.pdf.
Iraq. World Health Organization – Noncommunicable Diseases (NCD) Country Profiles, 2014.
Al-Kawaz AB (2010). Oral squamous cell carcinoma in Iraq: clinical analysis. MDJ. 2010;7(1):100-5.
Mohammed NA, Hussein AA, Majeed AH. Detection of Human Herpesvirus Type-1 Antigen in Tissues of Oral Squamous Cell Carcinoma by Direct Immunofluorecent Assay. Diyala J Med. 2015 Jun;8(2):38-45.
Mork J, Lie A K, Glattre E, Hallmans G, Jellum E, Koskela P, et al. Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med. 2001 Apr 12;344(15):1125-31.
Nishioka S, Fukushima K, Nishizaki K, Gunduz M, Tominaga S, Fukazawa M, et al. Human papillomavirus as a risk factor for head and neck cancers: a case-control study. Acta Otolaryngol. Suppl. 1999;540:77-80.
Oda D, Bigler L, Lee P, Blanton R. HPV immortalization of human oral epithelial cells: a model for carcinogenesis. Exp Cell Res. 1996 Jul 10;226(1):164-9.
Miller CS, Johnstone BM. Is oral infection with human papillomavirus (HPV) a risk factor for oral squamous cell carcinoma (OSCC)? Evidence-Based Dent. 2003 Jun 28;4(2):29. doi:10.1038/sj.ebd.6400171.
Syrjanen K, Syrjanen S, Lamberg M, Pyrhonen S, Nuutinen J. Morphological and immunohistochemical evidence suggesting human papillomavirus (HPV) involvement in oral squamous cell carcinogenesis. Int J Oral Surg. 1983 Dec;12(6):418-24.
Moberg M, Gustavsson I, Gyllensten U. Real-time PCR-based system for simultaneous quantification of human papillomavirus types associated with high risk of cervical cancer. J Clin Microbiol. 2003 Jul;41(7):3221-8.
Akrish S, Ben-Izhak O, Sabo E, Rachmiel A. Oral squamous cell carcinoma associated with proliferative verrucous leukoplakia compared with conventional squamous cell carcinoma--a clinical, histologic and immunohistochemical study. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015 Mar;119(3):318-25. doi: 10.1016/j.oooo.2014.10.023.
Stetler-Stevenson WG. The tumor microenvironment: regulation by MMP-independent effects of tissue inhibitor of metalloproteinases-2. Cancer Metastasis Rev, 2008 Mar;27(1):57-66.
Görögh T, Beier U H, Bäumken J, Meyer JE, Hoffmann M, Gottschlich S, et al. Metalloproteinases and their inhibitors: influence on tumor invasiveness and metastasis formation in head and neck squamous cell carcinomas. Head Neck. 2006 Jan;28:31-9.
Gillison ML. Human papillomavirus and prognosis of oropharyngeal squamous cell carcinoma: implications for clinical research in head and neck cancers. J Clin Oncol. 2006 Dec;24(36):5623-5.
Chandolia B, Basu SK, Kumar M. Can MMP-9 be a Prognosticator Marker for Oral Squamous Cell Carcinoma? J Clin Diagn Res. 2016 Jan;10(1):ZC09-13. doi: 10.7860/JCDR/2016/14128.7034.
Ali SHM, Al-Hijazi AY, Khashman BM (2011). P53-tumor suppressor gene overexpression in huma papilloma virus-infected patients with oral squamous cell carcinoma. J Bagh College Dentistry. 2011;23 (Spec Issue):70-6.
Jabar S, Sarkis S, Madjd Z, Kalantari E. The expression of p53 and mdm4 in oral, laryngeal and cutaneous squamous cell carcinoma; a comparative study by tissue microarray. Eur Scientif J, 2013 Dec;9(36):56-73.
Katayama A, Bandoh N, Kishibe K, Takahara M, Ogino T, Nonaka S, et al. Expressions of matrix metalloproteinases in early-stage oral squamous cell carcinoma as predictive indicators for tumor metastases and prognosis. Clin Cancer Res. 2004 Jan 15;10(2):634-40.
Lee SY, Park SY, Kim SH, Choi EC. Expression of matrix metalloproteinases and their inhibitors in squamous cell carcinoma of the tonsil and their clinical significance. Clin Exp Otorhinolaryngol. 2011 Jun;4(2):88-94.
Al-Salihi KA, Ang SL, Azlina A, Farini MS, Jaffar H. Immunohistochemical and molecular genetic analysis of p 53 in oral squamous cell carcinoma (scc) in Hospital University Science Malaysia: a preliminary study. Braz J Oral Sci. 2008 Jan-Mar;7(24):1476-83.
Mashhadiabbas F, Mahjour F, Mahjour SB, Fereidooni F, Hosseini FS. The immunohistochemical characterization of MMP-2, MMP-10, TIMP-1, TIMP-2, and podoplanin in oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 Aug;114(2):240-50. doi: 10.1016/j.oooo.2012.04.009.
Maheshwari V, Sharma SC, Narula V, Verma S, Jain A, Alam K. Prognostic and predictive impact of Ki67 in premalignant and malignant squamous cell lesion of oral cavity. Int J Head Neck Surg. 2013 May-Aug;4(2):61-5.
Ree AH, Florenes VA, Berg JP, Maelandsmo GM, Nesland JM, Fodstad O. High levels of messenger RNAs for tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in primary breast carcinomas are associated with development of distant metastases. Clin Cancer Res. 1997 Sep;3(9):1623-8.
Grimminger CM, Danenberg PV. Update of prognostic and predictive biomarkers in oropharyngeal squamous cell carcinoma: a review. Eur Arch Otorhinolaryngol. 2011 Jan;268(1):5-16. doi: 10.1007/s00405-010-1369-x.
Cardeal LB, Boccardo E, Termini L, Rabachini T, Andreoli MA, di Loreto C, et al. HPV16 oncoproteins induce mmps/reck-timp-2 imbalance in primary keratinocytes: possible implications in cervical carcinogenesis. PLoS One. 2012;7(3):e33585. doi: 10.1371/journal.pone.0033585.
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 Jan 20;95(1):44-50.
Pérez-Sayáns García M, Suárez-Peñaranda JM, Gayoso-Diz P, Barros-Angueira F, Gándara-Rey JM, García-García A (2012). Tissue inhibitor of metalloproteinases in oral squamous cell carcinomas - a therapeutic target? Cancer Lett. 2012 Oct 1;323(1):11-9. doi: 10.1016/j.canlet.2012.03.040.
Dürst M, Dzarlieva-Petrusevska RT, Boukamp P, Fusenig NE, Gissmann L. Molecular and cytogenetic analysis of immortalized human primary keratinocytes obtained after transfection with human papillomavirus type 16 DNA. Oncogene. 1987;1:(3):251-6.
Feller L, Wood NH, Khammissa RA, Lemmer J. Human papillomavirus-mediated carcinogenesis and HPV-associated oral and oropharyngeal squamous cell carcinoma. Part 2: Human papillomavirus associated oral and oropharyngeal squamous cell carcinoma. Head Face Med.n 2010 Jul 15;6:15. doi: 10.1186/1746-160X-6-15.
Zhu C, Ling Y, Dong C, Zhou X, Wang F. The relationship between oral squamous cell carcinoma and human papillomavirus: a meta-analysis of a Chinese population (1994–2011). PLoS One. 2012;7(5):e36294. doi: 10.1371/journal.pone.0036294.
McLaughlin-Drubin ME, Münger K (2009). Oncogenic activities of human papillomaviruses. Virus Res. 2009 Aug;143(2):195-208. doi: 10.1016/j.virusres.2009.06.008.
Ikebe T, Shinohara M, Takeuchi H, Beppu M, Kurahara S, Nakamura S, et al. Gelatinolytic activity of matrix metalloproteinase in tumor tissues correlates with the invasiveness of oral cancer. Clin Exp Metastasis. 1999 Jun;17(4):315-23.
O-charoenrat P, Rhys-Evans P, Eccles SA. Expression of matrix metalloproteinases and their inhibitors correlates with invasion and metastasis in squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg. 2001 Jul;127(7):813-20.
Grignon DJ, Sakr W, Toth M, Ravery V, Angulo J, Shamsa F, et al. High levels of tissue inhibitor of metalloproteinase-2 (TIMP-2) expression are associated with poor outcome in invasive bladder cancer. Cancer Res. 1996 Apr 1;56(7):1654-9.
Ondruschka C, Buhtz P, Motsch C, Freigang B, Schneider-Stock R, Roessner A, et al. Prognostic value of MMP-2, -9 and TIMP-1, -2 immunoreactive protein at the invasive front in advanced head and neck squamous cell carcinomas. Pathol Res Pract. 2002;198(8):509-15.
Sternlicht MD, Bissell MJ, Werb Z. The matrix metalloproteinase stromelysin-1 acts as a natural mammary tumor promoter. Oncogene. 2000 Feb 21;19(8):1102-13.
Lee JI, Jin BH, Kim MA, Yoon HJ, Hong SP, Hong SD. Prognostic significance of CXCR-4 expression in oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009 May;107(5):678-84. doi: 10.1016/j.tripleo.2008.12.047.
Qu H, Xin ZE, Jing X. Expression and correlation of MMP-2. TIMP-2 in oral squamous cell cancer. J Hard Tissue Biol. 2005;14(2):311-2.
Singh RD, Haridas N, Patel JB, Shah FD, Shukla SN, Shah PM, et al. Matrix metalloproteinases and their inhibitors: correlation with invasion and metastasis in oral cancer. 2010 Jul;25(3):250-9. doi: 10.1007/s12291-010-0060-8.
Blancato J, Singh B, Liu A, Liao DJ, Dickson RB. Correlation of amplification and overexpression of the c-myc oncogene in high–grade breast cancer: FISH, ISH and immunohistochemical analysis. Br J Cancer 2004 Apr 19;90(8):1612-9.
How to Cite
The Brazilian Journal of Oral Sciences uses the Creative Commons license (CC), thus preserving the integrity of the articles in an open access environment.