Fas and Fas ligand expression on germinal center type-diffuse large B-cell lymphoma is associated with the clinical outcome

Eur J Haematol. 2006 Jun;76(6):465-72. doi: 10.1111/j.1600-0609.2006.00631.x. Epub 2006 Feb 23.

Abstract

In recent years, diffuse large B-cell lymphoma (DLBCL) has been classified by DNA microarray analysis into the germinal center B-cell-like (GC) type, the activated B-cell-like (ABC) type and type 3. The latter two types can be collectively categorized as the non-GC (NGC) type. From the prognostic perspective, the GC type has a favorable clinical outcome when compared with the NGC type. The protein Fas induces apoptosis of lymphocytes by binding with the Fas ligand (FasL), and escape from such apoptosis is considered to lead to malignant transformation of the cells and unrestricted growth of lymphoma. We proposed a hypothesis that Fas/FasL expression could be possibly related with a better survival of GC type DLBCL and evaluated 69 DLBCL cases immunohistochemically with CD10, Bcl-6, MUM1, Fas and FasL. These lymphomas were classified as GC type (positive for CD10 or Bcl-6 and negative for MUM1) or NGC type. The GC type had a better overall survival rate than the NGC type (P = 0.0723). Among markers as given above, positive CD10 was the most significant prognostic factor for overall survival in total DLBCL (P < 0.05). In the GC type, Fas and FasL expressions were significantly associated with a favorable overall survival (Fas: P < 0.005; FasL: P < 0.05). Hence, Fas or FasL expression might contribute to a better prognosis of this type of DLBCL.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Apoptosis / physiology
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Biomarkers, Tumor / blood
  • Cyclophosphamide / administration & dosage
  • DNA-Binding Proteins / analysis
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives
  • Embryonal Carcinoma Stem Cells
  • Fas Ligand Protein
  • Female
  • Follow-Up Studies
  • Germinal Center / pathology
  • Humans
  • Interferon Regulatory Factors / analysis
  • L-Lactate Dehydrogenase / blood
  • Life Tables
  • Lymphoma, Large B-Cell, Diffuse / classification
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / genetics
  • Lymphoma, Large B-Cell, Diffuse / metabolism*
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Male
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / genetics
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Prednisolone / administration & dosage
  • Prognosis
  • Proportional Hazards Models
  • Proto-Oncogene Proteins c-bcl-6
  • Survival Analysis
  • Treatment Outcome
  • Tumor Necrosis Factors / biosynthesis*
  • Tumor Necrosis Factors / genetics
  • Vincristine / administration & dosage
  • fas Receptor / biosynthesis*
  • fas Receptor / genetics

Substances

  • BCL6 protein, human
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • FASLG protein, human
  • Fas Ligand Protein
  • Interferon Regulatory Factors
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-6
  • Tumor Necrosis Factors
  • fas Receptor
  • interferon regulatory factor-4
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisolone
  • L-Lactate Dehydrogenase

Supplementary concepts

  • VAP-cyclo protocol
  • VEP-THP protocol