Expression of Matrix Metalloproteinase-2/9 and Tissue Inhibitor of Metalloproteinase-1/2 as Predictive Factors in Oropharyngeal Squamous Cell Carcinoma

Document Type: Original

Authors

1 Department of Otolaryngology,Oncology and Oral and Maxillofacial Surgery, Faculty of Health Sciences, Nicolaus Copernicus University in Toruń, Poland.

2 Private ENT Practice, Bydgoszcz, Poland

3 Department of Clinical Pathomorphology Collegium Medicum, Faculty of Medicine, Nicolaus Copernicus University in Toruń, Poland

4 Department of Oncologic Pathology, Poznan University of Medical Sciences and Greater Poland Oncology Center, Poznan, Poland

Abstract

Introduction:
Metalloproteinases and their tissue inhibitors play an important role in the metastases formation.
A multistage process of carcinogenesis requires the involvement of numerous enzymes and compounds that facilitate the expansion of tumor cells. The formation of metastases depends on both metalloproteinases and tissue inhibitors activation leading to the activation of neoangiogenesis. The changes of the expression in stromal and tumor proteins could be prognostic factors in patients with oropharyngeal squamous cell carcinoma.
 
Materials and Methods:
This study was conducted on a total of 34 patients with squamous cell carcinoma of the oropharynx divided into 2 groups, including 20 patients with neck metastasis and 14 patients without lymph node metastasis. Immunohistochemistry was performed with a standard protocol.
 
Results:
The results of the present analysis indicated a higher expression of metalloproteinases 2 in the stroma than in tumor with increasing tumor grade. The dynamics of changes in the expression of metalloproteinases showed the increase in metalloproteinases 2 and the decrease in metalloproteinases 9 depending on the tumor size. Dynamics of changes in the expression of tissue inhibitor 1 in the tumor stroma significantly increased with the tumor stage. In the assessment of nodal staging from N0 to N3, the expression of tissue inhibitor 1 and 2 were higher in the tumor tissues. The increase of metalloproteinases 2, tissue inhibitor 1 in the tumor, and metalloproteinases 9 in the stroma were characterized by a reduction in the odds ratio of patient’s survival.
 
Conclusion:
The complex evaluation of the expression of metalloproteinases and tissue inhibitors may be used for the prognosis of the patient’s survival.

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Main Subjects


1. Rundhaug JE. Matrix metalloproteinases and angiogenesis. J Cell Mol Med. 2005; 9:267-85.

2. Stokes A, Joutsa J, Ala-Aho R, Pitchers M, Pennington CJ, Martin C. Expression profiles and clinical correlations of degradome components in the tumor microenvironment of Head and Neck Squamous Cell Carcinoma. Clin Cancer Res. 2010; 16: 2022-35.

3. Blavier L, Henreit P, Imren S, Declerck YA. Tissue inhibitors of matrix metalloproteinases in cancer. Ann NY Acad Sci. 1999; 878: 108-19.

4. Cao XL, Xu RJ, Zheng YY, Liu J, Teng YS, Li Y. Expression of type IV collagen, metalloproteinase-2, metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in laryngeal squamous cell carcinomas. Asian Pac J Cancer Preve. 2011; 12: 3245-9.

5. Lee KD, Lee HS, Jeon C.H. Body fluid biomarkers for early detection of Head and Neck Squamous Cell Carcinomas. Anticancer Res. 2011; 31: 1161-7.

6. Ma J, Wang J, Fan W, Pu X, Zhang D, Ch F. Upregulated TIMP-1 correlates with poor prognosis of laryngeal squamous cell carcinoma. Int J Clin Exp Pathol. 2014; 7: 246-54.

7. Mitra RS, Goto M, Lee JS, Maldonado M, Taylor JP, Pan Q. Rap1GAP promotes invasion via induction of matrix metalloproteinase 9 secretion, which is associated with poor survival in low N-stage squamous cell carcinoma. Cancer Res. 2008; 68: 3959–69.

8. Mohtasham N, Babakoohi S, Shiva A, Shadman A, Kamyab-Hesari K, Shakeri MT. Immunohistochemical study of p53, Ki-67, MMP-2 and MMP-9 expression at invasive front of squamous cell and verrucous carcinoma in oral cavity. Pathol Res Pract. 2013; 209: 110-4.

9. Rossano R, Larocca M, Riviello L, Coniglio MG, Vandooren J, Liuzzi GM.  Heterogeneity of serum gelatinases MMP-2 and MMP-9 isoforms and charge variants. J Cell Mol  Med. 2014; 18: 242-52.

10. Dünne AA, Gröbe A, Sesterhenn AM, Barth P, Dalchow C, Werner JA. Influence of matrix metalloproteinase 9 (MMP-9) on the metastatic behavior of oropharyngeal cancer. Anticancer Res. 2005; 25: 4129-34.

11. Fan HX, Li HX, Chen D, Gao ZX, Zheng JH. Changes in the expression of MMP2, MMP9, and ColIV in stromal cells in oral squamous tongue cell carcinoma: relationships and prognostic implications.J Exp Clin Cancer Res.2012;29: 31: 90.

12. Franchi A, Santucci M, Masini E, Sardi I, Paglierani M, Gallo O. Expression of matrix metalloproteinase 1, matrix metalloproteinase 2, and matrix metalloproteinase 9 in carcinoma of the head and neck. Cancer. 2002; 95: 1902-10.

13.Rosenthal EL, Matrisian LM. Matrix metalloproteases in head and neck cancer. Head Neck. 2006; 28: 639-48.

14. Hong SD, Hong SP, Lee JI, Lim CY. Expression of matrix metalloproteinase-2 and -9 in oral squamous cell carcinomas with regard to the metastatic potential. Oral Oncol. 2000; 36: 207-13.

15. Kurahara S, Shinohara M, Ikebe T, Nakamura S, Beppu M, Hiraki A. Expression of MMPS, MT-MMP, and TIMPs in squamous cell carcinoma of  the oral cavity: correlations with tumor invasion and metastasis. Head Neck. 1999;  21: 627-38.

16. Burduk PK, Bodnar M, Sawicki P, Szylberg L, Wissniewska E, Kazmierczak W et al. 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. 2015; 37: 418-22.

17. Yorioka CW, Coletta RD, Alves F, Nishimoto IN, Kowalski LP, Graner E. Matrix metalloproteinase-2 and -9 activities correlate with the disease-free survival of oral squamous cell carcinoma patients. Int J Oncol. 2002; 20: 189-94.

18. Fan H, Jiang W, Li H, Fang M, Xu Y, Zheng J. MMP-1/2 and TIMP-1/2 expression levels, and the levels of collagenous and elastic fibers correlate with disease progression in a hamster model of tongue cancer. Oncol Lett. 2016; 11: 63–8.