Increased Expression of Matrix Metalloproteinases 2 and 9 as Poor Prognosis Factor for Hodgkin’s Lymphoma Patients

Introduction Matrix metalloproteinases (MMPs) are zinc dependent endopeptidases that act on both renewal and remodeling of the extracellular matrix. Increased expression of these proteins is associated with neoplastic, invasive and metastatic processes. Studies show that in Hodgkin’s Lymphoma (HL), strong expression of metalloproteinase 2 (MMP-2) correlates with a favorable prognosis, while expression of metalloproteinase 9 (MMP-9) showed an adverse outcome. Therefore, the aim of our study was to evaluate the expression of MMP-2 and MMP-9 as a prognostic factor in patients diagnosed with HL.

Methods In the present study, 45 paraffin biopsies from patients up to 19 years old diagnosed with HL were used in two referral hospitals in the state of Pernambuco, Brazil. The immunohistochemistry reaction used primary monoclonal antibodies directed to matrix metalloproteinases (MMP-2 and -9) to detect such proteins in the tumor microenvironment.

Results MMP-2 intensity pattern was stronger (> 10% of total field) in patients with stage III/IV and B symptoms. MMP-2 x Risk group showed significant value (p=0,0388). That is, the stronger the MMP-2 marking, the greater the unfavorable risk. However for MMP-9 there was no difference in the stronger intensity pattern in relation to stages I/II and III/IV, only in the presence of symptoms B. The criterion MMP-9 x Symptoms B showed significant value (p = 0.0411). Therefore, patients with B symptoms have higher MMP-9 expression.

Conclusion Thus, we believe that both MMP-2 and MMP-9 can be considered poor prognostic molecules for Hodgkin’s lymphoma and the that RNA expression evaluation could confirm the results.

Conflict of Interest:

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this work.

• References

• 1 Sousa Madeira Campos R, Lopes A, Cardoso Guimarães G, Lopes Carvalho A, Augusto Soares F. E-cadherin, MMP-2, and MMP-9 as prognostic markers in penile cancer: Analysis of 125 patients. Urology. 2006; 67 (04) : 797-802.
• 2 Kuittinen O, Soini Y, Turpeenniemi-Hujanen T. Diverse role of MMP-2 and MMP-9 in the clinicopathological behavior of Hodgkin’s lymphoma. Eur J Haematol. 2002; 69 (04) : 205-12.
• 3 Li H, Qiu Z, Li F, Wang C. The relationship between MMP-2 and MMP-9 expression levels with breast cancer incidence and prognosis. Oncol Lett. 2017; 14 (05) : 5865-70.
• 4 Campos AH, Vassallo J, Soares FA. Matrix Metalloproteinase-9 Expression by Hodgkin-Reed-Sternberg Cells Is Associated with Reduced Overall Survival in Young Adult Patients with Classical Hodgkin Lymphoma. PLoS One. 2013; 8 (09) : 8-13.