A New Biological Model Based on Immunohistochemistry Predicts Survival in Patients with Diffuse Large B-Cell Lymphoma.
Anamarija M Perry, Paul N Meyer, Theresa M Cardesa-Salzmann, Lynette M Smith, Luis Colomo, Armando L Guillermo, Elias Campo, Timothy C Greiner, Jan Delabie, Randy D Gascoyne, Lisa Rimsza, Elaine S Jaffe, German Ott, Andreas Rosenwald, Rita M Braziel, Raymond Tubb, James Cook, Louis Staudt, Joseph Connors, Julie M Vose, Wing C Chan, Dennis D Weisenburger. University of Nebraska Medical Center for the Lymphoma/Leukemia Molecular Profiling Project, Omaha
Background: Gene expression profiling (GEP) has shown that the cell of origin and two stromal signatures (Stromal-1 and -2) are of prognostic importance in diffuse large B-cell lymphoma (DLBCL). Therefore, we attempted to simulate the GEP findings using immunohistochemical stains in paraffin-embedded tissue. Moreover, we constructed a new biological prognostic model for DLBCL based on our findings.
Design: Tissue microarrays (TMAs) of 252 cases of de novo DLBCL were analyzed. Cases were assigned a germinal center B-cell (GCB) or non-germinal center B-cell (non-GCB) phenotype using the Choi algorithm. The TMAs were stained with a SPARC antibody, for the Stromal-1 signature, and the percentage of positive histiocytes was estimated: low (<5%) and high (≥5%). The microvascular density (MVD), reflecting the Stromal-2 signature, was determined with a CD31 antibody by analyzing the digitalized image. MVD values were grouped, with quartiles 1-3 compared to quartile 4. Patients were divided by International Prognostic Index (IPI) scores as follows: low (0-2) and high (3-5). A biological prognostic model was built, using 192 cases with complete clinical data, by awarding one point for each adverse prognostic marker (non-GCB type, SPARC <5% and MVD quartile 4). The patients were assigned to one of three groups: 0-1, 2, and 3 points.
Results: Of the 252 patients, 77 had died and 175 were alive at the time of last follow-up. The median follow-up of the patients was 3.4 years (range, 0.1-11.3). By univariate analysis, the Choi algorithm, SPARC and MVD positivity were all highly significant predictors of overall survival (OS) and event-free survival (EFS). Multivariate analysis showed that the Choi algorithm (HR=2.1, p=0.058), SPARC (HR=2.9, p=0.0065), MVD (HR=3.8, p=0.0004) and the IPI (HR=2.1, p=0.042) were all independent predictors of OS and EFS. The new biological model was highly predictive of OS and EFS (p<0.001) with survival curves delineating patients with a good (score 0-1), intermediate (score 2) or poor prognosis (score 3).
Conclusions: All three biological markers (Choi algorithm, SPARC and MVD) were significant predictors of survival in multivariate analysis, independent of the IPI. The new, combined biological prognostic model derived from paraffin-embedded tissue was also highly predictive of OS and EFS, and could be used in conjunction with the IPI to stratify DLBCL patients for risk–adapted therapies.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 177, Monday Morning