Clin Exp Otorhinolaryngol.  2015 Mar;8(1):57-64. 10.3342/ceo.2015.8.1.57.

Characteristics of Expression of Matrix Metalloproteinases (MMP-2 and MMP-9) in Glottic Squamous Cell Carcinoma and Benign Vocal Fold Lesions

Affiliations
  • 1Department of Otorhinolaryngology, Lithuanian University of Health Sciences, Kaunas, Lithuania. vikisl@yahoo.com
  • 2Department of Pathology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
  • 3Laboratory of Molecular Cardiology in the Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania.

Abstract


OBJECTIVES
The aim of this study was to investigate expression profile of matrix metalloproteinases (MMP-2 and MMP-9) in glottic squamous cell carcinoma (SCC) and benign vocal fold lesions (BVFLs) and to correlate it with clinical and pathological features.
METHODS
The immunohistochemical expression of MMP-2 and MMP-9 was investigated in specimens taken from 217 patients group, including vocal fold polyps (n=39), recurrent respiratory papillomatosis (n=30), laryngeal keratosis (n=36), glottic SCC (n=112), and the normal tissue of vocal fold (n=12, control group). The expression of MMP-2 and MMP-9, both in epithelium and stroma cells, was graded on a semiquantitative scale, ranging from 0 (no expression) to 18 points (high expression).
RESULTS
Expressions of both, MMP-2 and MMP-9 were significantly higher in the glottic SCC group comparing with BVFL group. Significant higher expression of parenchymal MMP-2 (P<0.001) and stromal MMP-9 (P=0.01) was revealed in the group of moderate/poorly differentiated glottic SCC comparing with well differentiated glottic SCC group. Expression of stroma MMP-2 was found to be correlated with nodal metastasis (P=0.030). Expressions of both, MMP-2 and MMP-9 were not correlated with clinical stage, tumor T value, smoking, alcohol use, age in the glottic SSC patients group. The MMP-2 stroma value of 11.2 points was determined as the optimum point (limiting value) for separating BVFL and glottic SCC patient groups.
CONCLUSION
Our results suggest that expressions of both MMP-2 and MMP-9 are up-regulated already in the development of BVFL, the next determinant step is concerned with occurrence of malignization. Limiting value of stroma MMP-2 demonstrates prognostic importance of MMP-2 in glottic SCC carcinogenesis.

Keyword

Matrix Metalloproteinases; Laryngeal Neoplasms; Lymph Nodes; Neoplasm Metastasis

MeSH Terms

Carcinogenesis
Carcinoma, Squamous Cell*
Epithelium
Humans
Keratosis
Laryngeal Neoplasms
Lymph Nodes
Matrix Metalloproteinases*
Neoplasm Metastasis
Papilloma
Polyps
Smoke
Smoking
Vocal Cords*
Matrix Metalloproteinases
Smoke

Figure

  • Fig. 1 Immunohistochemical expression of MMP-9, MMP-2 in samples from glottic squamous cell carcinoma (×20). Neoplastic epithelial/parenchyma (white arrow) and stroma cells (black arrow) demonstrate high expression of MMP-9 (A) and high expression of MMP-2 in stroma cells and moderate expression in epithelial/parenchyma cells (B). MMP, matrix metalloproteinase.

  • Fig. 2 Graphical comparison of MMP-2 expression (boxes represent medians and 25%-75% of cases) among glottic SCC and benign vocal fold lesions patients' groups. MMP, matrix metalloproteinase; SCC, squamous cell carcinoma; LK, laryngeal keratosis; VFP, vocal fold polyps; RRP, recurrent laryngeal papillomas.

  • Fig. 3 Graphical comparison of MMP-9 expression (boxes represent medians and 25%-75% of cases) among glottic SCC and benign focal fold lesions patients' groups. MMP, matrix metalloproteinase; SCC, squamous cell carcinoma; LK, laryngeal keratosis; VFP, vocal fold polyps; RRP, recurrent laryngeal papillomas.


Reference

1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007; Jan-Feb. 57(1):43–66. PMID: 17237035.
Article
2. Ward EC, Van As-Brooks C. Head and neck cancer: treatment, rehabilitation, and outcomes. San Diego (CA): Plural Publishing;2007.
3. Rudolph E, Dyckhoff G, Becher H, Dietz A, Ramroth H. Effects of tumour stage, comorbidity and therapy on survival of laryngeal cancer patients: a systematic review and a meta-analysis. Eur Arch Otorhinolaryngol. 2011; 2. 268(2):165–179. PMID: 20957488.
Article
4. Zhang H, Liu M, Sun Y, Lu J. MMP-14 can serve as a prognostic marker in patients with supraglottic cancer. Eur Arch Otorhinolaryngol. 2009; 9. 266(9):1427–1434. PMID: 19283401.
Article
5. Tan CT, Chu CY, Lu YC, Chang CC, Lin BR, Wu HH, et al. CXCL12/CXCR4 promotes laryngeal and hypopharyngeal squamous cell carcinoma metastasis through MMP-13-dependent invasion via the ERK1/2/AP-1 pathway. Carcinogenesis. 2008; 8. 29(8):1519–1527. PMID: 18487224.
Article
6. Liu Y, Li Y, Liu Z, Zhang L, Anniko M, Duan M. Prognostic significance of matrix metalloproteinase-20 overexpression in laryngeal squamous cell carcinoma. Acta Otolaryngol. 2011; 7. 131(7):769–773. PMID: 21466263.
Article
7. 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; 6. 4(2):88–94. PMID: 21716956.
Article
8. Vihinen P, Ala-aho R, Kahari VM. Matrix metalloproteinases as therapeutic targets in cancer. Curr Cancer Drug Targets. 2005; 5. 5(3):203–220. PMID: 15892620.
Article
9. Sarioglu S, Ozer E, Kirimca F, Sis B, Pabuccuoglu U. Matrix metalloproteinase-2 expression in laryngeal preneoplastic and neoplastic lesions. Pathol Res Pract. 2001; 197(7):483–486. PMID: 11482578.
10. Bogusiewicz M, Stryjecka-Zimmer M, Szymanski M, Rechberger T, Golabek W. Activity of matrix metalloproteinases-2 and -9 in advanced laryngeal cancer. Otolaryngol Head Neck Surg. 2003; 1. 128(1):132–136. PMID: 12574771.
Article
11. Peschos D, Damala C, Stefanou D, Tsanou E, Assimakopoulos D, Vougiouklakis T, et al. Expression of matrix metalloproteinase-9 (gelatinase B) in benign, premalignant and malignant laryngeal lesions. Histol Histopathol. 2006; 6. 21(6):603–608. PMID: 16528670.
12. Christopoulos TA, Papageorgakopoulou N, Ravazoula P, Mastronikolis NS, Papadas TA, Theocharis DA, et al. Expression of metalloproteinases and their tissue inhibitors in squamous cell laryngeal carcinoma. Oncol Rep. 2007; 10. 18(4):855–860. PMID: 17786346.
Article
13. Bartlett RS, Heckman WW, Isenberg J, Thibeault SL, Dailey SH. Genetic characterization of vocal fold lesions: leukoplakia and carcinoma. Laryngoscope. 2012; 2. 122(2):336–342. PMID: 22252855.
Article
14. Liu WW, Zeng ZY, Wu QL, Hou JH, Chen YY. Overexpression of MMP-2 in laryngeal squamous cell carcinoma: a potential indicator for poor prognosis. Otolaryngol Head Neck Surg. 2005; 3. 132(3):395–400. PMID: 15746850.
Article
15. Karahan N, Baspinar S, Yariktas M, Kapucuoglu N. Matrix Metalloproteinases (MMP-2 and MMP-9) and cyclooxygenase-2 (COX-2) expressions in vocal fold polyps. J Voice. 2009; 1. 23(1):29–33. PMID: 17624726.
Article
16. 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; 1. 10(2):634–640. PMID: 14760086.
Article
17. Gorogh T, Beier UH, Baumken 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; 1. 28(1):31–39. PMID: 16265652.
Article
18. Whittaker M, Ayscough A. Matrix metalloproteinases and their inhibitors: current status and future challenges. Celltransmissions. 2001; 2. 17(1):3–14.
19. Nelson AR, Fingleton B, Rothenberg ML, Matrisian LM. Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol. 2000; 3. 18(5):1135–1149. PMID: 10694567.
Article
20. Danilewicz M, Sikorska B, Wagrowska-Danilewicz M. Prognostic significance of the immunoexpression of matrix metalloproteinase MMP2 and its inhibitor TIMP2 in laryngeal cancer. Med Sci Monit. 2003; 3. 9(3):MT42–MT47. PMID: 12640351.
21. Jodele S, Blavier L, Yoon JM, DeClerck YA. Modifying the soil to affect the seed: role of stromal-derived matrix metalloproteinases in cancer progression. Cancer Metastasis Rev. 2006; 3. 25(1):35–43. PMID: 16680570.
Article
22. Wittekindt C, Jovanovic N, Guntinas-Lichius O. Expression of matrix metalloproteinase-9 (MMP-9) and blood vessel density in laryngeal squamous cell carcinomas. Acta Otolaryngol. 2011; 1. 131(1):101–106. PMID: 20873997.
Article
23. Hanata K, Yamaguchi N, Yoshikawa K, Mezaki Y, Miura M, Suzuki S, et al. Soluble EMMPRIN (extra-cellular matrix metalloproteinase inducer) stimulates the migration of HEp-2 human laryngeal carcinoma cells, accompanied by increased MMP-2 production in fibroblasts. Arch Histol Cytol. 2007; 12. 70(5):267–277. PMID: 18431027.
Article
24. Xie M, Sun Y, Li Y. Expression of matrix metalloproteinases in supraglottic carcinoma and its clinical implication for estimating lymph node metastases. Laryngoscope. 2004; 12. 114(12):2243–2248. PMID: 15564854.
Article
25. Roepman P, Kemmeren P, Wessels LF, Slootweg PJ, Holstege FC. Multiple robust signatures for detecting lymph node metastasis in head and neck cancer. Cancer Res. 2006; 2. 66(4):2361–2366. PMID: 16489042.
Article
26. Yuce I, Bayram A, Cagli S, Canoz O, Bayram S, Guney E. The role of CD44 and matrix metalloproteinase-9 expression in predicting neck metastasis of supraglottic laryngeal carcinoma. Am J Otolaryngol. 2011; Mar-Apr. 32(2):141–146. PMID: 20434807.
27. Mallis A, Teymoortash A, Mastronikolis NS, Werner JA, Papadas TA. MMP-2 expression in 102 patients with glottic laryngeal cancer. Eur Arch Otorhinolaryngol. 2012; 2. 269(2):639–642. PMID: 21667117.
Article
28. Ruokolainen H, Paakko P, Turpeenniemi-Hujanen T. Expression of matrix metalloproteinase-9 in head and neck squamous cell carcinoma: a potential marker for prognosis. Clin Cancer Res. 2004; 5. 10(9):3110–3116. PMID: 15131051.
29. Kosunen A, Pirinen R, Ropponen K, Pukkila M, Kellokoski J, Virtaniemi J, et al. CD44 expression and its relationship with MMP-9, clinicopathological factors and survival in oral squamous cell carcinoma. Oral Oncol. 2007; 1. 43(1):51–59. PMID: 16798062.
Article
30. Sun Y, Liu M, Yang B, Li B, Lu J. Role of siRNA silencing of MMP-2 gene on invasion and growth of laryngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol. 2008; 11. 265(11):1385–1391. PMID: 18437407.
Article
Full Text Links
  • CEO
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr