Thymidine Phosphorylase Expression in B Cell Lymphomas and Its Significance: A New Prognostic Marker?
Xingcao Nie, Peter M Clifford, Rekha Bhat, Rebecca Heintzelman, Mini Abraham, J Steve Hou. Drexel University College of Medicine, Philadelphia
Background: Thymidine phosphorylase (TP) is noted to be expressed by both tumor and stromal cells in a variety of cancers. Few studies of TP expression have been reported in hematopoietic malignancies. Our earlier study found that TP is expressed by malignant T cells in mycosis fungoides. The objective of this study is to explore TP expression and its significance in B cell lymphomas.
Design: Paraffin blocks from follicular lymphoma (FL, grade 1-2, 18 cases, grade 3, 10 cases), diffuse large B cell lymphoma (DLBCL, 28 cases) and 9 benign lymph nodes were used for a tissue microarray. Immunohistochemical (IHC) staining (TP and CD68) was used. In DLBCL, IHC prognostic markers (CD10, Bcl-6, Mum-1) were performed. Correlation of TP expression in DLBCL indirectly with prognostic immunomarkers and directly with survival data was applied.
Results: 1. TP is positive in malignant B cells with a cytoplasmic pattern in a subset of B cell lymphomas. Reactive lymphocytes are negative. TP expression in higher-grade DLBCL and FL3, represents 68% (25/38) and 60% (6/10) respectively, compared to 11% (2/18) in lower-grade FL1-2; comparing TP positivity in FL3 and DLBCL (66%, 25/38) to FL1-2 (11%), it approaches statistical significance. 2. TP stains macrophages/stromal cells with an intenser cytoplasmic and/or nuclear pattern in both lymphoma and benign lymph nodes. CD68 highlights this pattern. Of note, increased numbers of macrophage/stromal cells in higher-grade lymphomas are associated with enhanced TP staining in neoplastic B cells (observation only). 3. Within TP positive DLBCL, the majority of the cases (13/19, 68%) are of non-germinal center origin, which is known to indicate a poorer prognosis compared to germinal center origin. There is also a direct correlation between TP expression in malignant B cells and overall worse patient survival in DLBCL.
Conclusions: 1. TP is more likely expressed by malignant B cells in higher grade lymphoma. 2. TP expression in B cell lymphomas may be due to changes intrinsic to the tumor cells and/or it may reflect interactions between the microenvironment and the tumor cells. Previous studies noted that the mechanism of TP in tumorigenesis is inhibition of the apoptosis pathway in tumor cells and stimulation of tumor angiogenesis by tumor and stromal cells via the PI3K/mTOR pathway. The exact mechanism of TP expression in B cell lymphoma needs further investigation. 3. In DLBCL, TP positivity in lymphoma cells seems to correlate with non-germinal center origin and a worse patient outcome. However, this observation needs additional cases for confirmation.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 193, Tuesday Afternoon