Immunostains for C-MYC and BCL2 Protein Predict Survival in Patients with Diffuse Large B-Cell Lymphoma Treated with Rituximab
Anamarija Perry, Yuridia Alvarado-Bernal, Javier Laurini, Lynette Smith, Kai Fu, Patricia Aoun, Timothy Greiner, Wing Chan, Philip Bierman, Gregory Bociek, James Armitage, Julie Vose, Dennis Weisenburger. University of Nebraska, Omaha, NE
Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, and the addition of rituximab to standard chemotherapy has confounded the use of prognostic markers such as Ki67 and BCL2. The impact of C-MYC expression on the prognosis of DLBCL is also unclear, especially when coupled with Ki67 and BCL2. Therefore, we investigated the expression of these three proteins in paraffin-embedded tissue, including their interaction and influence on the survival of DLBCL patients.
Design: Tissue microarray slides from 105 cases of de novo DLBCL treated with rituximab and CHOP or CHOP-like therapies were stained using antibodies against GCET1, CD10, BCL6, MUM1, FOXP1, BCL2, C-MYC and Ki67. The tumors were assigned a germinal center B-cell-like (GCB) or non-GCB subtype according to the Choi algorithm for cell of origin. Positivity for BCL2, C-MYC and Ki67 was graded in 10% increments by two pathologists. The Kaplan-Meyer method was used to estimate overall survival (OS) and event-free survival (EFS), and the log-rank test was used to compare the survival distributions. Cox regression analysis was used to compare OS and EFS in multivariate analysis after adjusting for the International Prognostic Index (IPI) and cell of origin.
Results: Among the 105 patients, 58 (55%) were male and 47 (45%) were female, with a median age of 62 years. By univariate analysis, the IPI, cell of origin, and BCL2 and C-MYC expression were significant predictors of OS and EFS, whereas Ki67 was not predictive. In multivariate analysis, C-MYC was an independent predictor of OS (p=0.013), whereas BCL2 was a significant predictor of OS and EFS in the low IPI group (p=0.015 and p=0.0007, respectively). Survival analysis showed that patients who had both BCL2<30% and C-MYC<50% had the best prognosis, whereas the patients with BCL2≥30% and C-MYC≥50% had the worst outcome. In multivariate analysis, the combination of the BCL2 and C-MYC was an independent predictor of OS and EFS (p=0.016 and p=0.006, respectively). The risk of death was 8.7 times greater in cases with BCL2≥30% and C-MYC≥50% as compared to those with BCL2<30% and C-MYC<50%.
Conclusions: In patients with DLBCL, high expression of C-MYC and BCL2 is a predictor of poor survival. Immunohistochemistry for C-MYC and BCL2 is a useful method for risk stratification of patients with DLBCL.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 221, Monday Morning