SRPK1 and SRPK2: Potential Diagnostic Marker for Diffuse Large B-Cell Lymphoma
Parham Minoo, Xiang-Dong Fu, Huan-You Wang. University of California San Diego, San Diego, CA
Background: SRPK1 and SRPK2 are members of mammalian serine-arginine protein kinase family of proteins involved in the regulation of RNA splicing. SRPK1 and SRPK2 are expressed in variety of cell lines and tissues. Aberrant RNA splicing is a characteristic of malignant cells; however the exact underlying mechanism is not well understood. Altered expression of SRPK proteins has been shown in many cancers including breast, colon and pancreatic carcinoma and retinoblastoma. Furthermore, downregulation of SRPK-1 in advanced cases of retinoblastoma is associated with development of resistance to cisplatin-based chemotherapy. The expression of SRPK proteins in malignant lymphoma has not been examined.
Design: SRPK1 and SRPK2 expressions were analyzed using immunohistochemistry in 24 lymph nodes with diffuse large B-cell lymphoma (DLBCL), 15 lymph nodes with small lymphocytic lymphoma (SLL), and 29 reactive lymph nodes with no evidence of DLBCL or SLL.
Results: SRPK1 and SRPK2 expressions were found in 62.5% and 54.2% of DLBCL cases, respectively. SRPK expression was mainly cytoplasmic in all positive cases. In contrast, none of the SLL cases showed any expression of SRPK1 and only 13% (2/15) showed SRPK2 expression. All of the reactive lymph nodes in control group were interpreted as negative for both SRPK1 and 2 expressions. However, in some of the reactive lymph nodes, a very faint staining was found in mantle zone cells and immunoblasts. These findings indicate that SRPK1 and SRPK2 are significantly upregulated in DLBCL compared to SLL (p<0.0001 for SRPK-1 and p=0.008 for SRPK-2). There was no association between SRPK positivity and germinal center immunophenotype in DLBCL group (p<0.5).
Conclusions: SRPK1 and SRPK2 are upregulated in the majority of diffuse large B-cell lymphoma cases, which can be used as a diagnostic marker. In addition, elevated SRPK expression can be used as an indicator of sensitivity to platinum-based therapeutic agents in refractory DLBCL patients who failed regular therapy. Further studies are underway to study the expression profiles of SRPK1 and 2 in other B-cell non-Hodgkin lymphomas.
Monday, March 4, 2013 1:00 PM
Poster Session II # 193, Monday Afternoon