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The potential role of MMP-9 and VEGF-C as predictors of lymph node involvement in papillary thyroid carcinoma

  • Sonar Soni Panigoro ,
  • Muhammad ,
  • Diani Kartini ,
  • Bob Andinata ,
  • Boy Subirosa Sabarguna ,
  • Agnes Stephanie Harahap ,


Abstract

Introduction: Most thyroid malignancy is papillary thyroid carcinoma (PTC). However, lymph node metastases occur in 30-40% of PTC patients. Biomarkers to predict cervical lymph node metastases have now begun to be widely varied, such as matrix metalloproteinase (MMP) and vascular endothelial growth factor (VEGF). There has not been any diagnostic agreement on MMP-9 and VEGF-C as predictors of lymph node metastasis in PTC. Hence, this study aims to determine the association of MMP-9 and VEGF-C to cervical lymph node metastases in PTC patients.

Methods: A cross-sectional study was conducted at Cipto Mangunkusumo General Hospital, Jakarta. Patients diagnosed with PTC based on histopathological examination were included in this study. Patients with distant metastases were excluded from the study. The expression of MMP-9 and VEGF-C was investigated at the Anatomical Pathology Laboratory.

Results: Sixty-two patients were included in this study, 80.6% female and 19.4% male. The MMP-9 expression was higher in the metastatic group (p<0.001). The same results were also found in VEGF-C expression, where the median expression of this marker in the metastatic group was higher than in the non-metastatic group (p<0.001). We found a significant positive correlation between the MMP-9 and VEGF-C expressions (correlation coefficient of 0.618).

Conclusions: There is a significant relationship between the expression of MMP-9 and VEGFC with cervical lymph node metastases in PTC patients. The MMP-9 and VEGF-C expression was higher in the metastatic group. The increased MMP-9 expression is also positively correlated with increased VEGF-C expression.

Keywords: Lymph node metastases MMP-9 papillary thyroid carcinoma. VEGF-C

References

  1. Lukitto P, Manoppo A, Azamris. Protokol penatalaksanaan tumor / kanker tiroid. Jakarta: PERABOI; 2003.
  2. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1–133.
  3. Lal G, Clark O. Thyroid, parathyroid, and adrenal. In: Brunicardi F, editor. Schwartz's principles of surgery. 11th ed. USA: McGraw-Hill Education; 2019. p. 1643 – 63.
  4. Tian X, Cong M, Zhou W, Zhu J, Liu Q. Relationship between protein expression of VEGF-C, MMP-2 and lymph node metastasis in papillary thyroid cancer. J Int Med Res. 2008;36(4):699–703.
  5. Shindo ML, Caruana SM, Kandil E, McCaffrey JC, Orloff LA, Porterfield JR, et al. Management of invasive well-differentiated thyroid cancer: an American Head and Neck Society consensus statement. AHNS consensus statement. Head Neck. 2014;36(10):1379–90.
  6. Zhang Y, Luo YK, Zhang MB, Li J, Li CT, Tang J, et al. Values of ultrasound features and MMP-9 of papillary thyroid carcinoma in predicting cervical lymph node metastases. Sci Rep. 2017;7(1):1–8. Available from: http://dx.doi.org/10.1038/s41598-017-07118-7
  7. Folgueras AR, Pendás AM, Sánchez LM, López-Otín C. Matrix metalloproteinases in cancer: from new functions to improved inhibition strategies. Int J Dev Biol. 2004;48(5–6):411–24.
  8. Selemetjev S, Ðoric I, Paunovic I, Tatic S, Cvejic D. Coexpressed High Levels of VEGF-C and Active MMP-9 Are Associated With Lymphatic Spreading and Local Invasiveness of Papillary Thyroid Carcinoma. Am J Clin Pathol. 2016;146(5):594–602.
  9. Maeta H, Ohgi S, Terada T. Protein expression of matrix metalloproteinases 2 and 9 and tissue inhibitors of metalloproteinase 1 and 2 in papillary thyroid carcinomas. Virchows Arch. 2001;438(2):121–8.
  10. Tanaka K, Kurebayashi J, Sonoo H, Otsuki T, Yamamoto Y, Ohkubo S, et al. Expression of vascular endothelial growth factor family messenger RNA in diseased thyroid tissues. Surg Today. 2002;32(9):761–8.
  11. Liang H, Zhong Y, Luo Z, Huang Y, Lin H, Luo M, et al. Assessment of biomarkers for clinical diagnosis of papillary thyroid carcinoma with distant metastasis. Int J Biol Markers. 2010;25(1):38–45.
  12. Zarkesh M, Zadeh-Vakili A, Akbarzadeh M, Fanaei SA, Hedayati M, Azizi F. The role of matrix metalloproteinase-9 as a prognostic biomarker in papillary thyroid cancer. BMC Cancer. 2018;18(1):1199.
  13. Marecko I, Cvejic D, Selemetjev S, Paskas S, Tatic S, Paunovic I, et al. Enhanced activation of matrix metalloproteinase-9 correlates with the degree of papillary thyroid carcinoma infiltration. Croat Med J. 2014;55(2):128–37.
  14. Wang N, Jiang R, Yang J-Y, Tang C, Yang L, Xu M, et al. Expression of TGF-β1, SNAI1 and MMP-9 is associated with lymph node metastasis in papillary thyroid carcinoma. J Mol Histol. 2014;45(4):391–9.
  15. Feng W, Jia S. Rapamycin inhibits the invasive ability of thyroid cancer cells by down-regulating the expression of VEGF-C in vitro. Cell Biochem Funct. 2012;30(6):487–91.
  16. Mohamad Pakarul Razy NH, Wan Abdul Rahman WF, Win TT. Expression of Vascular Endothelial Growth Factor and Its Receptors in Thyroid Nodular Hyperplasia and Papillary Thyroid Carcinoma: A Tertiary Health Care Centre Based Study. Asian Pac J Cancer Prev. 2019;20(1):277–82.
  17. Plate KH, Breier G, Millauer B, Ullrich A, Risau W. Up-regulation of vascular endothelial growth factor and its cognate receptors in a rat glioma model of tumor angiogenesis. Cancer Res. 1993;53(23):5822–7.
  18. Schoenberger J, Grimm D, Kossmehl P, Infanger M, Kurth E, Eilles C. Effects of PTK787/ZK222584, a tyrosine kinase inhibitor, on the growth of a poorly differentiated thyroid carcinoma: an animal study. Endocrinology. 2004;145(3):1031–8.
  19. Quintero-Fabián S, Arreola R, Becerril-Villanueva E, Torres-Romero JC, Arana-Argáez V, Lara-Riegos J, et al. Role of Matrix Metalloproteinases in Angiogenesis and Cancer. Front Oncol. 2019;9:1370.
  20. Vandooren J, Van den Steen PE, Opdenakker G. Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9): the next decade. Crit Rev Biochem Mol Biol. 2013;48(3):222–72.

How to Cite

Panigoro, S. S., Muhammad, Kartini, D., Bob Andinata, Sabarguna, B. S., & Harahap, A. S. (2023). The potential role of MMP-9 and VEGF-C as predictors of lymph node involvement in papillary thyroid carcinoma. Bali Medical Journal, 12(1), 187–191. https://doi.org/10.15562/bmj.v12i1.3805
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Sonar Soni Panigoro
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Muhammad
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Diani Kartini
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Bob Andinata
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Boy Subirosa Sabarguna
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Agnes Stephanie Harahap
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