Differential Expression of STAT-6 and Activated STAT-6 in Primary Central Nervous System Lymphoma and Peripheral Diffuse Large B-Cell Lymphoma
NT Sherwood, JF Silverman, C Pu, K Ru. Allegheny General Hospital, Pittsburgh, PA
Background: STAT-6 is a protein transcription factor and member of the signal transduction and activator of transcription (STAT) family. These cytoplasmic proteins become phosphorylated and activated by Janus kinase in response to extracellular cytokines. The phosphorylated STAT protein is then transported to the nucleus where it exerts activation of transcription. STAT6 overexpression has been reported in central nervous system (CNS) B-cell lymphoma by DNA microarray studies. Our aim was to explore the expression level of STAT6 and activated STAT6 (pSTAT6) by immunohistochemical studies in CNS B-cell lymphoma and compared to peripheral diffuse large B-cell lymphoma (DLBCL) and investigate STAT6 activation in the tumorigenesis of these two types of lymphomas.
Design: Paraffin embedded surgical specimens including 14 cases of peripheral DLBCL and 8 cases of primary CNS B-cell lymphoma were retrieved from our files. All cases were stained with STAT6 and pSTAT6. The slides were then reviewed, and staining patterns were recorded as negative, partially positive (weak or focal staining), and strongly positive.
Results: Strongly positive staining for both STAT6 and pSTAT6 were seen in 8 of 8 cases (100%) of primary CNS B-cell lymphoma. As expected, staining was cytoplasmic for STAT6 and nuclear for pSTAT6. Only 3 of 14 cases (21%) of DLBCL were strongly and diffusely positive for either stain. There was weak, focal, or partial staining for STAT6 in 2 of 14 (14%) cases and also for pSTAT6 in 6 of 14 (43%) cases of DLBCL.
Conclusions: The STAT6 and pSTAT6 markers were highly sensitive for detecting primary CNS B-cell lymphoma. The staining patterns were strongly and diffusely positive in all cases of primary CNS B-cell lymphoma. Only 3 of 14 cases of DLBCL exhibited this pattern. The remaining cases of DLBCL were either completely negative or exhibited focal, weak, or partial-positive staining. Median survival for DLBCL may be as high as 5 years depending on subtype, whereas the median survival for primary CNS B-cell lymphoma may be as low as 12-18 months. This may reflect differences in their respective tumorigenesis and related to the STAT6 activation pathway. It would be worthwhile to further investigate this phenomenon with a longitudinal study comparing survival in cases of DLBCL that are strongly positive for STAT6 versus those that are negative or only partially positive. Additionally, STAT6 and pSTAT6 may have a role in future targeted therapy for aggressive CNS B-cell.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 236, Tuesday Afternoon