[1230] Differential Expression of RanGAP1 between Reactive and Neoplastic B-Cell Proliferations: Using Comparative Proteomics to Search Lymphoma Biomarker and Its Clinicopathologic Role.

Kung-Chao Chang, Hsiang-Lin Song, Chien-Hun Huang, Chen Chang, Ying-Tai Jin. National Cheng Kung University and Hospital, Tainan, Taiwan; Taiwan Adventist Hospital, Taipei, Taiwan

Background: Tumor biomarkers play a pivotal role in screening, diagnosis, and follow-up of disease. Lymphoma markers may also contribute to treatment strategy, prognostic stratification, and study of tumorigenesis. Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphomas, accounts for 30% to 40% of all lymphoma cases. However, long-term survival by current chemotherapy was achieved in only 40% of patients, warranting the development of novel therapeutic strategies. Of them, immunotherapy is the most promising. Thus, the lymphoma-specific biomarkers (lymphoma-specific antigens) can also serve as the targets for the immunotherapy.
Design: By comparative proteomics analysis of two DLBCL cell lines with a lymphoblastoid cell line (LCL), we found RanGAP1 (Ran GTPase-activating protein 1) differentially expressed between DLBCL and B-cell hyperplasia that was validated on immunoblotting.
Results: In addition, immunostaining showed that the majority of DLBCLs (92%, 46/50) were RanGAP1-positive, in contrast to reactive lymphoid hyperplasia (n=12), which revealed RanGAP1 positivity only in germinal center cells. Interestingly, serum level of RanGAP1 was also higher in DLBCL patients (n = 50) than normal populations (n = 36)(3.83 ± 2.76 ng/mL vs. 2.43 ± 1.98 ng/mL, p = 0.0074). For other B-cell lymphomas, RanGAP1 was frequently expressed in tumors with brisk mitotic activity (B-lymphoblastic lymphoma/leukemia, 93.3% and Burkitt lymphoma, 94.6%) or with cell cycle aberrations (mantle cell lymphoma, 83.3% and Hodgkin lymphoma, 90.5%).

Results of RanGAP1 immunostaining in other B-cell lymphomas
Lymphoma typesNo.Positivity(%)M/FAge (mean)
B-lymphoblastic lymphoma/leukemia1514/1593.3%10/534.9
Small lymphocytic lymphoma161/166.3%12/464.9
Mantle cell lymphoma1210/1283.3%11/167.3
Follicular lymphoma174/1723.5%9/856.9
Marginal zone lymphoma, MALT type305/3016.7%13/1760.1
Lymphoplasmacytic lymphoma114/1136.4%9/273.5
Burkitt lymphoma3735/3794.6%25/126.0
Hodgkin lymphoma4238/4290.5%34/86.7
MALT: mucosa-associated lymphoid tissue


Conclusions: Although, RanGAP1 bore no prognostic significance, it may be a candidate DLBCL marker applicable for lymphoma management and novel therapeutic strategy.
Category: Hematopathology

Wednesday, March 2, 2011 1:00 PM

Poster Session VI # 210, Wednesday Afternoon

 

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