Study Of Immunohistochemical Subgroups, Molecular Genetic Alterations And Their Correlations To Prognosis In Chinese Patients With Diffuse Large B Cell Lymphoma

Objectives:1.To evaluate the reliability of Hans algorithm.2. To study the prognosticimpact of microenvironment in patients with DLBCL.3. To investigate rearrangementof three important genes and overexpression of the targeting proteins and evaluate theirprognostic significance in DLBCL.Materials and Methods:1. Immunohistochemical analysis for CD10, Bcl-6, MUM1,SPARC, CD68and CD31were performed on tissue microarray specimen of79cases ofde novo DLBCL from PLA General Hospital. Different immunophenotypic subgroupswere classified according to Hans algorithm, expression of SPARC or microvessledensity (MVD), and the prognostic impact was assessed respectively.2.79DLBCLwere investigated using IHC and FISH to detect protein overexpression andrearrangement of MYC, BCL2and BCL6. Prognostic significance of MYC, BCL2andBCL6was assessed respectively.Results:1. Univariate analysis of the clinical data of79DLBCL patients found that thePFS was worse in older age, advanced stage, high IPI score and high ECOG score.Univariate analysis also found that OS was worse in Elevated serum LDH, high IPIscore and high ECOG score (p<0.05).2. Patients with high SPARC positivity in themicroenvironment had a significantly longer OS and PFS(OS: p=0.02；PFS: p=0.01).Multivariate analysis revealed that SPARC expression predicted patient PFSindependent of the IPI. Patients with high MVD in the microenvironment had asignificantly shorter OS and PFS (OS: p=0.03；PFS: p=0.01). Multivariate analysisrevealed that high MVD predicted patient survival independent of the IPI. Hansalgorithm shed no statistically significant difference.3. Patients with MYCtranslocation showed a significantly shorter OS and PFS(OS: p=0.00；PFS: p=0.02).Multivariate analysis revealed that MYC translocation predicted patient OS independentof the IPI. Patients with c-MYC overexpression showed a significantly shorter OS and PFS(OS: p=0.00； PFS: p=0.00). Multivariate analysis revealed that c-MYCoverexpression predicted patient survival independent of the IPI. The proteinoverexpression and rearrangement for BCL2or BCL6did not have prognosticsignificance.4. One case named “double-hit” lymphoma and another case named“triple-hit” lymphoma were discovered.Conclusions:1. In a variety of clinical factors, high IPI score was a poor prognosticfactor.2. SPARC, MVD were independent predictors of OS and PFS, whereas the Hansalgorithm was not a prognostic factor. SPARC expression predict good outcome,whereas high MVD predict poor outcome.3. Both rearrangement of MYC andoverexpression of c-MYC were independent predictors of OS and PFS.40%or morec-MYC positive tumor cells could be the optimal cutoff.4. BCL2and BCL6could notpredictive prognosis, not only in molecular level, but also in protein level.