Expression of Matrix Metalloproteinase 2 and Tissue Inhibitor of Metalloproteinase 2 in Papillary Microcarcinoma of the Thyroid Gland are Not Related with Extrathyroid Invasion, Multifocality and Lymph Node Metastasis of the Tumor

갑상선 유두상미세암종에서 갑상선외 침윤, 다원성 및 경부전이에 대한 Matrix Metalloproteinase 2 및 Tissue Inhibitor of Matrix Metalloproteinase 2 발현의 의의 : 부정적 결과 보고

  • Choi Seung-Ho (Departments of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Nam Soon-Yuhl (Departments of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Cho Kyung-Ja (Departments of Pathology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim Sang-Yoon (Departments of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine)
  • 최승호 (울산대학교 의과대학 서울아산병원 이비인후과학교실) ;
  • 남순열 (울산대학교 의과대학 서울아산병원 이비인후과학교실) ;
  • 조경자 (울산대학교 의과대학 서울아산병원 병리학교실) ;
  • 김상윤 (울산대학교 의과대학 서울아산병원 이비인후과학교실)
  • Published : 2005.11.01

Abstract

Objectives: To investigate the role of MMP-2 and TIMP-2 in the invasion and metastasis of thyroid papillary microcarcinomas. Materials and Methods: We performed immunohistochemical study on MMP-2 and its tissue inhibitor (TIMP-2) using tissue microarrays containing 2 cores of 40 microPTC and 8 non-neoplastic thyroid tissue. The expression intensity was semiquantitatively scored as -, ${\pm}$, +1, +2, and +3. Results: Both MMP-2 and TIMP-2 expression was observed in all tumors(100%) and in 1 of 8 non-neoplastic tissue(12.5%), and the positive staining was restricted to the epithelial cells. In 17 and 23 tumors with or without extrathyroid invasion, respectively, 8(47%) and 10(43%) cases showed moderate to strong(+23) positivity for MMP-2. TIMP-2 expression was moderate to strong in 13 cases(76%) and 16 cases(70%) in each group. In multifocal and solitary tumors, 3 of 6(50%) and 11 of 21(52%) cases showed moderate to strong MMP-2 expression, and 5/6(83%) and 15/21(71%) showed moderate to strong TIMP-2 expression. Conclusion: There is no relationship between MMP-2 or TIMP-2 expression and extrathyroid invasion or tumor multifocality in papillary microcarcinoma of the thyroid gland.

Keywords

References

  1. Chambers AF, Matrisian LM: Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst. 1997; 89 (17):1260-270 https://doi.org/10.1093/jnci/89.17.1260
  2. Kurahara S, Shinohara M, Ikebe T, et al: 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 (7):627-638 https://doi.org/10.1002/(SICI)1097-0347(199910)21:7<627::AID-HED7>3.0.CO;2-2
  3. Imanishi Y, Fujii M, Tokumaru Y, et al: Clinical significance of expression of membrane type I matrix metalloproteinase and matrix metalloproteinase-2 in human head and neck squamous cell carcinoma. Hum Pathol. 2000;31 (8):895-904 https://doi.org/10.1053/hupa.2000.9756
  4. Stetler-Stevenson WG, Aznavoorian S, Liotta LA: Tumor cell interactions with the extracellular matrix during invasion and metastasis. Annu Rev Cell Biol. 1993;9:541-573 https://doi.org/10.1146/annurev.cb.09.110193.002545
  5. Nomura H, Fujimoto N, Seiki M, Mai M, Okada Y: Enhanced production of matrix metalloproteinases and activation of matrix metalloproteinase 2 (gelatinase A) in human gastric carcinomas. Int J Cancer. 1996;69 (1):9-16 https://doi.org/10.1002/(SICI)1097-0215(19960220)69:1<9::AID-IJC3>3.0.CO;2-8
  6. 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):121-128 https://doi.org/10.1007/s004280000286
  7. Korem S, Kraiem Z, Shiloni E, Yehezkel O, Sadeh O, Resnick MB: Increased expression of matrix metalloproteinase-2: a diagnostic marker but not prognostic marker of papillary thyroid carcinoma. Isr Med Assoc J. 2002;4 (4):247-251
  8. Baldini E, Toller M, Graziano PM, Russo FP, Pepe M, Biordi L, et al: Expression of matrix metalloproteinases and their specific inhibitors in normal and different human thyroid tumor cell lines. Thyroid. 2004;14 (11):881-888 https://doi.org/10.1089/thy.2004.14.881
  9. Nakamura H, Ueno H, Yamashita K, et al: Enhanced production and activation of progelatinase A mediated by membrane-type 1 matrix metalloproteinase in human papillary thyroid carcinomas. Cancer Res. 1999;59 (2):467-473
  10. Pelizzo MR, Boschin IM, Toniato A, et al: Natural history, diagnosis, treatment and outcome of papillary thyroid microcarcinoma (PTMC): a mono-institutional 12-year experience. Nucl Med Commun. 2004;25 (6):547-552 https://doi.org/10.1097/01.mnm.0000126625.17166.36
  11. Matrisian LM: The matrix-degrading metalloproteinases. Bioessays. 1992;14 (7):455-463 https://doi.org/10.1002/bies.950140705
  12. Azzam HS, Arand G, Lippman ME, Thompson EW: Association of MMP-2 activation potential with metastatic progression in human breast cancer cell lines independent of MMP-2 production. J Natl Cancer Inst. 1993;85 (21):1758-1764 https://doi.org/10.1093/jnci/85.21.1758
  13. Kameyama K: Expression of MMP-1 in the capsule of thyroid cancer-relationship with invasiveness. Pathol Res Pract. 1996; 192 (1):20-26 https://doi.org/10.1016/S0344-0338(96)80125-7
  14. Zedenius J, Stahle-Backdahl M, Enberg U, Grimelius L, Larsson C, Wallin G, et al: Stromal fibroblasts adjacent to invasive thyroid tumors: expression of gelatinase A but not stromelysin 3 mRNA. World J Surg. 1996;20 (1):101-106 https://doi.org/10.1007/s002689900018
  15. Campo E, Merino MJ, Liotta L, Neumann R, Stetler-Stevenson W: Distribution of the 72-kd type N collagenase in nonneo-plastic and neoplastic thyroid tissue. Hum Pathol. 1992;23 (12): 1395-1401 https://doi.org/10.1016/0046-8177(92)90060-G
  16. Albini A, Melchiori A, Santi L, Liotta LA, Brown PD, Stetler-Stevenson WG: Tumor cell invasion inhibited by TIMP-2. J Natl Cancer Inst. 1991;83 (11):775-779 https://doi.org/10.1093/jnci/83.11.775
  17. Imren S, Kohn DB, Shimada H, Blavier L, DeClerck YA: Overexpression of tissue inhibitor of metalloproteinases-2 retroviral-mediated gene transfer in vivo inhibits tumor growth and invasion. Cancer Res. 1996;56 (13):2891-2895
  18. Yu AE, Hewitt RE, Kleiner DE, Stetler-Stevenson WG: Molecular regulation of cellular invasion-role of gelatinase A and TIMP-2. Biochem Cell Biol. 1996;74 (6):823-831 https://doi.org/10.1139/o96-088
  19. Grignon DJ, Sakr W, Toth M, 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; 56 (7):1654-1659
  20. Visse R, Nagase H: Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res. 2003;92 (8):827-839 https://doi.org/10.1161/01.RES.0000070112.80711.3D