title: 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.
authors.affiliation: Department of Oncology and Radiotherapy, University of Oulu and Oulu University Hospital, Oulu, Finland. heli@kyllonen.fi
authors.forename: Heli
authors.initials: H
authors.lastname: Kyllönen
authors.forename: Anna Kaisa
authors.initials: AK
authors.lastname: Pasanen
authors.forename: Outi
authors.initials: O
authors.lastname: Kuittinen
authors.forename: Kirsi-Maria
authors.initials: KM
authors.lastname: Haapasaari
authors.forename: Taina
authors.initials: T
authors.lastname: Turpeenniemi-Hujanen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D018858:Germinal Center / Q000473:pathology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009367:Neoplasm Staging; D011239:Prednisolone / Q000008:administration & dosage; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D000069283:Rituximab; D015996:Survival Rate; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D009363:Neoplasm Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D000069283:Rituximab; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D011241:Prednisone