Lack of prognostic value of MMP-9 expression and immunohistochemically defined germinal center phenotype in patients with diffuse large B-cell lymphoma treated with modern chemotherapy with or without CD20 antibody

Abstract

Diffuse large B-cell lymphomas (DLBCLs) are a heterogeneous group of lymphomas, with no accepted biological prognostic markers in routine clinical practice. Previously, matrix metalloproteinase (MMP-9), tissue inhibitors of matrix metalloproteinase (TIMP)- 1 and non-germinal center (GC) phenotype have been shown to associate with poor prognosis in DLBCL patients. The aim of this study was to find out whether tissue expression of gelatinases (MMP-2 and MMP-9) or their tissue inhibitors (TIMP-1 and TIMP-2) or immunohistochemically defined GC phenotype could act as prognostic markers in patients treated with modern treatments. Additionally, correlations between these proteins and GC phenotype were investigated. GC phenotype and tissue expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 were analyzed by immunohistochemistry in tissue samples from 114 DLBCL patients. In this study, in patients treated with modern lymphoma treatments (5-year cause-specific survival 69.8%) MMP-2, MMP-9, TIMP-1 or TIMP-2 expression or GC phenotype did not correlate with survival. International Prognostic Index (IPI) and stage were the only factors, which retained their prognostic significance in this patient material. Gelatinases or TIMPs did not correlate with GC phenotype, either. Prognostic markers are dependent on the lymphoma treatments used. In DLBCL patients treated with modern chemotherapy with or without rituximab, MMP-9, TIMP-1 and GC phenotype seem to have lost their prognostic value.

Overexpression of Matrix Metalloproteinase-21 is Associated with Poor Overall Survival of Patients with Colorectal Cancer

“…It has been proved that, compared with patients who did not receive 5-Fu based chemotherapy, patients treated with 5-Fu would lose the prognostic value of MMP-9. 46 Therefore, only patients who had not received neoadjuvant chemotherapy were recruited in our present study in order to diminish the influence of the neoadjuvant on MMPs and survival of patients.…”

Prediction of Colorectal Cancer Relapse and Prognosis by Tissue mRNA Levels of NDRG2

“…Considering Myc and its downstream regulated gene NDRG2 were also regulated by NF-kB pathway, the recruited patients who had received neoadjuvant chemotherapy would thus come up with false results. It has been proved that compared with patients who did not receive 5-FU-based chemotherapy, in patients treated with 5-FU, matrix metalloproteinase-9 would lose its prognostic value (48). So patients who had received neoadjuvant chemotherapy were excluded.…”

Matrix metalloproteinase‐9 is associated with disease‐free survival and overall survival in patients with gastric cancer

“…It has been proved that compared to patients who did not receive 5-Fu based chemotherapy, when patients treated with 5-Fu, MMP-9 would lost its prognostic value. 43 Therefore, in our study, the expression of MMP-9 was examined in patients who had not received neoadjuvant chemotherapy. Moreover, study on sensitivity analysis showed that recurrence or survival of patients after surgery was differentially extended by whether the patient received initial adjuvant therapy or not, the association between prognostic value of biomarkers on disease-free and overall survival at all time points could be substantially diminished.…”