Matrix metalloproteinase-9 is consistently expressed in Hodgkin/Reed-Sternberg cells and has no impact on survival in patients with Epstein–Barr virus (EBV)-related and non-related Hodgkin lymphoma in Brazil

Abstract

Clinical and histological features of classical Hodgkin lymphoma (cHL) are primarily due to the effects of cytokines and enzymes produced by Hodgkin/Reed-Sternberg (HRS) cells and their surrounding inflammatory cells. In EBV-related cancers, the expression of viral latent membrane protein 1 correlates with an increased MMP9 expression. In this study, we evaluated the prognostic relevance of MMP9 expression and EBV status in HRS cells in patients with cHL in Brazil. We selected 97 patients with cHL for EBV and MMP9 detection. EBV was detected in 52.5%, and MMP9 expression positivity was found in 87.6%. Of all cases, there was no correlation between MMP9 expression and EBV status. Response to treatment and relapse rate was independent of MMP9 expression and EBV status. MMP9 positivity did not influence overall survival and event-free survival. The consistent and increased intensity of MMP9 expression in HRS cells make this enzyme a potential target for therapy.

Matrix Metalloproteinase-9 Expression by Hodgkin-Reed-Sternberg Cells Is Associated with Reduced Overall Survival in Young Adult Patients with Classical Hodgkin Lymphoma

“…The expression of MMP9 has been associated with increased aggressiveness and poor prognosis in patients with non-Hodgkin lymphoma [10], but an influence on prognosis has not been reported in the few studies on cHL [11]–[13]. Flavell et al [11] reported that the survival analysis performed on their cases was compromised by the fact that there were a small number of patients in the MMP9-positive group, although there was a tendency toward an adverse outcome in this category.…”

“…The MMP9 antibody used in our study was the same used by Souza et al [13] in their study with 97 Brazilian patients, although the dilution was different (1∶100 versus 1∶200). Additionally, differences in immunohistochemical staining evaluation and the use of TMA in our study might have accounted for the discrepant results regarding the prognostic relevance of MMP9.…”

“…Additionally, differences in immunohistochemical staining evaluation and the use of TMA in our study might have accounted for the discrepant results regarding the prognostic relevance of MMP9. Souza et al [13] analyzed patients over 18 years old. Using the same approach, we also did not observe influence of MMP9 expression by neoplastic cells in cHL on overall survival, although there was a trend toward worse prognosis (P = 0.0681, Hazard ratio = 2.1745, 95% CI = 0.9901 to 4.7757).…”

“…One of them is the inclusion of patients treated with ABVD or ABVD-equivalent regimens, with a small number of patients treated with BEACOPP, although this approach has already been used in other studies [3],[13],[24]. Additionally, bias in statistical analysis, such as “overfitting” [25], could have existed.…”

“…MMP9 expression is also known to be mediated by Epstein-Barr virus infection [8],[9], which is associated with cHL in about 40% of cases [1],[2]. The expression of MMP9 has been related to a poorer prognosis in non-lymphoid tumors and in non-Hodgkin lymphoma [10], but lack of association has been reported in cHL, including a recent Brazilian study with 97 patients [11]–[13].…”