Abnormal Wnt Signaling and Stem Cell Activation in Reactive and Low-Grade Marginal Zone Lymphoma
D Zhang, MF O'Neil, MT Cunningham, F Fan, LH Li. University of Kansas Medical Center, Kansas City, KS; Stowers Institute, Kansas City, MO
Background: The variable natural history of MALT lymphoma poses challenge in predicting the clinical outcome. Since the Wnt singling, as indicated by nuclear localization of b-catenin, is believed to be a key in stem cell activation and stem cell self-renewal we explored the possibly that it might have a predictive value in marginal zone lymphoma . We chose to analyze pb-catS552 because its nuclear localization by immunohistochemistry appears to coincide with Wnt signaling initiated tumorigenesis in intestinal and hematopoietic tissues.
Design: Wnt signaling and activation was studied in 22 tissue samples of extranodal marginal zone lymphoma, atypical lymphoid hyperplasia, reactive lymphoid hyperplasia, and normal lymphoid tissue to determine if the Wnt signaling could help us distinguishing MALT lymphoma from the benign lesion. An anti-p- b-cat-S552 antibody has been developed to detect the phosphorylation of b-catenin at Ser-552. Immunohistochemical staining was performed. b-cat-S552 positive nuclear stained cells in the lymphoid areas were counted randomly under 40x objectives for 10 fields and the total number of positive cells was calculated.
Results: Compared to normal or reactive lymphoid tissue we found increased nuclear expression of localized b-catenin-pS552 in atypical lymphoid hyperplasia and extranodal marginal zone lymphoma. There was a statistically significant difference between reactive lymphoid hyperplasia, atypical lymphoid hyperplasia and marginal zone lymphoma (P<0.05). We followed sequentially three patients with stomach MALT lymphoma and studied their biopsies before and after treatment. The pβ-cat-S552 positive cells showed a decrease in number in response to the therapy for H. pylori, which also correlated with histologic remission.
Conclusions: In summary, we have demonstrated that β-cat-S552 positive nuclear stain cells were increased in number in atypical lymphoid hyperplasia and MALT lymphoma. Furthermore, we showed that these cells are located outside of germinal centers. We suggest that the antibody to β-cat-S552 can be used to assess the distribution and number of atypical lymphoid cells in the diagnosis of MALT lymphoma and for monitoring of those patients' response to therapy.
Monday, March 22, 2010 1:00 PM
Poster Session II # 163, Monday Afternoon