Advertisement

Tumor Biology

, Volume 36, Issue 11, pp 8593–8600 | Cite as

Matrix metalloproteinase-12 expression is increased in cutaneous melanoma and associated with tumor aggressiveness

  • Zixi Zhang
  • Shaojun Zhu
  • Yang Yang
  • Xianjie Ma
  • Shuzhong Guo
Research Article

Abstract

Cutaneous melanoma is the most malignant form of skin cancer characterized by aggressive invasion. Matrix metalloproteinases play essential roles in tumor invasion due to their ECM degrading capacity. However, the clinical significance of matrix metalloproteinasis (MMP)-12 in human cutaneous melanoma has not been addressed yet. In the present study, we investigated MMP-12 expression level in 298 patients with cutaneous melanoma and 60 normal skin tissue specimens by immunohistochemistry assay. Appropriate statistical analysis was utilized to determine the association of MMP-12 with clinical features and prognosis of melanoma. Results showed that MMP-12 expression was increased in cutaneous melanoma compared with that in normal skin. It was also found that MMP-12 expression in melanoma was significantly associated with tumor invasion and metastasis. Univariate survival analysis indicated that patients with melanoma of high MMP-12 expression had unfavorable overall survival compared with those of low MMP-12 expression. Cox’s proportional hazards analysis showed that MMP-12 expression was an independent prognostic marker of overall survival for patients with cutaneous melanoma. These results proved that MMP-12 expression was increased in cutaneous melanoma and associated with tumor progression. It also provided the first evidence that MMP-12 level could be an independent prognostic marker for patients with cutaneous melanoma.

Keywords

MMP-12 Melanoma Immunohistochemistry Progression Prognosis 

Notes

Acknowledgments

The present study is supported by the National Natural Science Foundation of China (No.: 30371469, 30672189, 30830102).

Conflicts of interests

None

References

  1. 1.
    Miller AJ, Mihm Jr MC. Melanoma. N Engl J Med. 2006;355:51–65.CrossRefPubMedGoogle Scholar
  2. 2.
    Rastrelli M, Alaibac M, Stramare R, Chiarion Sileni V, Montesco MC, Vecchiato A, et al. Melanoma m (zero): diagnosis and therapy. ISRN Dermatol. 2013;2013:616170.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA: Cancer J Clin. 2015;65:5–29.Google Scholar
  4. 4.
    Turner RM, Bell KJ, Morton RL, Hayen A, Francken AB, Howard K, et al. Optimizing the frequency of follow-up visits for patients treated for localized primary cutaneous melanoma. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29:4641–6.CrossRefGoogle Scholar
  5. 5.
    Curti BD. Rapid evolution of combination therapy in melanoma. N Engl J Med. 2014;371:1929–30.CrossRefPubMedGoogle Scholar
  6. 6.
    Luke JJ, Ott PA. New developments in the treatment of metastatic melanoma—role of dabrafenib-trametinib combination therapy. Drug Healthcare Patient Safety. 2014;6:77–88.CrossRefGoogle Scholar
  7. 7.
    Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Ding S, Byrd DR, et al. Multivariate analysis of prognostic factors among 2,313 patients with stage iii melanoma: comparison of nodal micrometastases versus macrometastases. J Clin Oncol: Off J Am Soc Clin Oncol. 2010;28:2452–9.CrossRefGoogle Scholar
  8. 8.
    Okwan-Duodu D, Pollack BP, Lawson D, Khan MK. Role of radiation therapy as immune activator in the era of modern immunotherapy for metastatic malignant melanoma. Am J Clin Oncol. 2015;38:119–25.CrossRefPubMedGoogle Scholar
  9. 9.
    Fogarty GB, Hong A. Radiation therapy for advanced and metastatic melanoma. J Surg Oncol. 2014;109:370–5.CrossRefPubMedGoogle Scholar
  10. 10.
    Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, et al. Genetic basis for clinical response to ctla-4 blockade in melanoma. N Engl J Med. 2014;371:2189–99.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Ai F, Zhang X, Li X, Qin Z, Ye Q, Tian L, Tang A, Li N, Li G, Ma J, Shen S. Up-regulation of matrix metalloproteinases in a mouse model of chemically induced colitis-associated cancer: The role of micrornas. Oncotarget. 2015;6:5412-25.Google Scholar
  12. 12.
    Zeng XH, Ou ZL, Yu KD, Feng LY, Yin WJ, Li J, et al. Absence of multiple atypical chemokine binders (acbs) and the presence of vegf and mmp-9 predict axillary lymph node metastasis in early breast carcinomas. Med Oncol. 2014;31:145.CrossRefPubMedGoogle Scholar
  13. 13.
    Yang X, Dong Y, Zhao J, Sun H, Deng Y, Fan J, et al. Increased expression of human macrophage metalloelastase (mmp-12) is associated with the invasion of endometrial adenocarcinoma. Pathol Res Pract. 2007;203:499–505.CrossRefPubMedGoogle Scholar
  14. 14.
    Asano T, Tada M, Cheng S, Takemoto N, Kuramae T, Abe M, et al. Prognostic values of matrix metalloproteinase family expression in human colorectal carcinoma. J Surg Res. 2008;146:32–42.CrossRefPubMedGoogle Scholar
  15. 15.
    Kahlert C, Fiala M, Musso G, Halama N, Keim S, Mazzone M, et al. Prognostic impact of a compartment-specific angiogenic marker profile in patients with pancreatic cancer. Oncotarget. 2014;5:12978–89.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Zheng J, Chu D, Wang D, Zhu Y, Zhang X, Ji G, et al. Matrix metalloproteinase-12 is associated with overall survival in chinese patients with gastric cancer. J Surg Oncol. 2013;107:746–51.CrossRefPubMedGoogle Scholar
  17. 17.
    Ng KT, Qi X, Kong KL, Cheung BY, Lo CM, Poon RT, et al. Overexpression of matrix metalloproteinase-12 (mmp-12) correlates with poor prognosis of hepatocellular carcinoma. Eur J Cancer. 2011;47:2299–305.CrossRefPubMedGoogle Scholar
  18. 18.
    Hagemann T, Gunawan B, Schulz M, Fuzesi L, Binder C. Mrna expression of matrix metalloproteases and their inhibitors differs in subtypes of renal cell carcinomas. Eur J Cancer. 2001;37:1839–46.CrossRefPubMedGoogle Scholar
  19. 19.
    Gorrin Rivas MJ, Arii S, Furutani M, Harada T, Mizumoto M, Nishiyama H, et al. Expression of human macrophage metalloelastase gene in hepatocellular carcinoma: Correlation with angiostatin generation and its clinical significance. Hepatology. 1998;28:986–93.CrossRefPubMedGoogle Scholar
  20. 20.
    Yang W, Arii S, Gorrin-Rivas MJ, Mori A, Onodera H, Imamura M. Human macrophage metalloelastase gene expression in colorectal carcinoma and its clinicopathologic significance. Cancer. 2001;91:1277–83.CrossRefPubMedGoogle Scholar
  21. 21.
    Hofmann HS, Hansen G, Richter G, Taege C, Simm A, Silber RE, et al. Matrix metalloproteinase-12 expression correlates with local recurrence and metastatic disease in non-small cell lung cancer patients. Clin Cancer Res: Off J Am Assoc Cancer Res. 2005;11:1086–92.Google Scholar
  22. 22.
    Kerkela E, Ala-aho R, Klemi P, Grenman S, Shapiro SD, Kahari VM, et al. Metalloelastase (mmp-12) expression by tumour cells in squamous cell carcinoma of the vulva correlates with invasiveness, while that by macrophages predicts better outcome. J Pathol. 2002;198:258–69.CrossRefPubMedGoogle Scholar
  23. 23.
    Kerkela E, Ala-Aho R, Jeskanen L, Rechardt O, Grenman R, Shapiro SD, et al. Expression of human macrophage metalloelastase (mmp-12) by tumor cells in skin cancer. J Investig Dermatol. 2000;114:1113–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Deraco M, Cabras A, Baratti D, Kusamura S. Immunohistochemical evaluation of minichromosome maintenance protein 7 (mcm7), topoisomerase iialpha, and ki-67 in diffuse malignant peritoneal mesothelioma patients using tissue microarray. Ann Surg Oncol. 2015. doi: 10.1245/s10434-015-4498-z.
  25. 25.
    Faraj SF, Chaux A, Gonzalez-Roibon N, Munari E, Cubilla AL, Shih Ie M, et al. Immunohistochemical expression of arid1a in penile squamous cell carcinomas: a tissue microarray study of 112 cases. Hum Pathol. 2015;46:761–6.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol: Off J Am Soc Clin Oncol. 2009;27:6199–206.CrossRefGoogle Scholar
  27. 27.
    Dummer R, Hauschild A, Guggenheim M, Keilholz U, Pentheroudakis G, Group EGW. Cutaneous melanoma: esmo clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol: Off J Eur Soc Med Oncol / ESMO. 2012;23 Suppl 7:vii86–91.CrossRefGoogle Scholar
  28. 28.
    Bilimoria KY, Raval MV, Bentrem DJ, Wayne JD, Balch CM, Ko CY. National assessment of melanoma care using formally developed quality indicators. J Clin Oncol: Off J Am Soc Clin Oncol. 2009;27:5445–51.CrossRefGoogle Scholar
  29. 29.
    Diaz-Cano SJ. Molecular mechanisms in melanoma. N Engl J Med. 2006;355:1395. author reply 1396.CrossRefPubMedGoogle Scholar
  30. 30.
    Nabha SM, dos Santos EB, Yamamoto HA, Belizi A, Dong Z, Meng H, et al. Bone marrow stromal cells enhance prostate cancer cell invasion through type I collagen in an mmp-12 dependent manner. Int J Cancer J Int du Cancer. 2008;122:2482–90.CrossRefGoogle Scholar
  31. 31.
    Laurenzana A, Biagioni A, D'Alessio S, Bianchini F, Chilla A, Margheri F, et al. Melanoma cell therapy: endothelial progenitor cells as shuttle of the mmp12 upar-degrading enzyme. Oncotarget. 2014;5:3711–27.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Zixi Zhang
    • 1
  • Shaojun Zhu
    • 2
  • Yang Yang
    • 1
  • Xianjie Ma
    • 1
  • Shuzhong Guo
    • 1
  1. 1.Department of Plastic Surgery, Xijing HospitalThe Fourth Military Medical UniversityXi’anChina
  2. 2.Department of Pathology, Tangdu HospitalThe Fourth Military Medical UniversityXi’anChina

Personalised recommendations