GCB vs. ACB Protein Signature in Mantle Cell Lymphoma (MCL). MUM1 Expression Correlate with Proliferation Index (Ki-67) without Impact on Survival
Rabeya Zarrin, Lesley Street, Farid Kosari, Payam Pournazari, Meer-Taher Shabani-Rad, Jay Patel, Douglas A Stewart, Adnan Mansoor. University of Calgary/Calgary Laboratory Services (CLS), Calgary, AB, Canada; University of Calgary, Calgary, AB, Canada
Background: MCL is a lymphoid malignancy with t(11;14) (q13;q32) leading to the aberrant expression of cyclin-D1. MCL is believed to originate from naive B-cell. A subset of MCL with expression of germinal centre (GC) associated proteins (CD10/ BCL6) or post GC protein (MUM1) has been reported. MCL have also displayed mutated V(H) genes in some reports. Since, Germinal Centre associated B-cell (GCB) vs. activated B-cell (ACB) protein signature correlate with prognosis in Diffuse large B-cell lymphoma, we screened a cohort of MCL for a variety of specific GC associated proteins. We also compared GCB vs. ACB protein signature in MCL with independent known prognostic factor (Ki-67) to determine if any of GCB vs. ACB protein expression has any correlation with proliferation index or prognosis.
Design: WHO (2008) criteria were utilized for diagnosis (CD20/5/D1+). Triplicate cores (1mm) of FFPE diagnostic tissue were used to create tissue microarray (TMA). 4 micron thick sections were stained with monoclonal antibodies (CD10/Bcl6/MUM1/ LMO2/HGAL/Ki-67) according to standard protocol. Staining among >30% cells were scored positive, irrespective of staining intensity. High proliferation index was considered as Ki67 positivity among >30% neoplastic cells. Two paired student t test or Fisher exact tests was used for correlations with p<0.05 being considered significant.
Results: 62 pts (37-88 yrs, mean 62; median 59; M:F 4.6:1) were included. 7/62 (11%) showed GCB protein CD10 expression (Hans et al) while 38/62(62%) had ACB type (MUM1+) protein signature. Bcl6 positivity was noted only in 9/62 (14%); all of these patients were positive for MUM1 protein. None of the samples (0/62) were positive for LMO2 or HGAL. 36/62 (56%) had high Ki 67. Proliferation index did not correlate with GCB associated protein expression (p 0.987) or ACB (p 1.009) protein signature. MUM1 expression correlated well with Ki-67 expression (p=<0.0003); however, MUM1 expression did not imapct over all survival (p 0.178).
Conclusions: Our data indicate that CD10 and Bcl6 protein expression is seen in a subset of MCL but more specific GC markers (HGAL and LMO2) are not expressed in MCL. A significant proportion of MCL pts show expression of MUM1 protein, which is associated with high proliferation index. However, expression of MUM1 do not impact overall survival in MCL.
Monday, March 19, 2012 1:00 PM
Poster Session II # 194, Monday Afternoon