Aberrant expression of the dendritic cell marker TNFAIP2 by the malignant cells of Hodgkin lymphoma and primary mediastinal large B-cell lymphoma distinguishes these tumor types from morphologically and phenotypically similar lymphomas.
ABSTRACT Tumor necrosis factor-α-inducible protein-2 (TNFAIP2) is a protein upregulated in cultured cells treated with tumor necrosis factor α (TNF), but its expression in normal and neoplastic tissues remains largely unknown. Here, we use standard immunohistochemical techniques to demonstrate that TNFAIP2 is normally expressed by follicular dendritic cells, interdigitating dendritic cells, and macrophages but not by lymphoid cells in secondary lymphoid tissues. Consistent with this expression pattern, we found strong TNFAIP2 staining of tumor cells in 4 of 4 cases (100%) of follicular dendritic cell sarcoma and in 3 of 3 cases (100%) of histiocytic sarcoma. Although TNFAIP2 is not expressed by the small and intermediate-sized neoplastic B cells comprising follicular lymphoma, small lymphocytic lymphoma, mantle cell lymphoma, or marginal zone lymphoma, we observed strong TNFAIP2 staining of the large, neoplastic cells in 31 of 31 cases (100%) of classical Hodgkin lymphoma, in 12 of 12 cases (100%) of nodular lymphocyte-predominant Hodgkin lymphoma, and in 27 of 31 cases (87%) of primary mediastinal (thymic) large B-cell lymphoma. In contrast, TNFAIP2 was expressed by malignant cells in only 2 of 45 cases (4%) of diffuse large B-cell lymphoma, not otherwise specified, in 2 of 18 cases (11%) of Burkitt lymphoma, and in 1 of 19 cases (5%) of anaplastic large cell lymphoma. Further analysis indicates that TNFAIP2, as a single diagnostic marker, is more sensitive (sensitivity=87%) and specific (specificity=96%) than TRAF1, nuclear cRel, or CD23 for distinguishing the malignant B cells of primary mediastinal (thymic) large B-cell lymphoma from those of its morphologic and immunophenotypic mimic, diffuse large B-cell lymphoma, not otherwise specified. Thus, TNFAIP2 may serve as a useful new marker of dendritic and histiocytic sarcomas, the aberrant expression of which in the malignant cells of classical Hodgkin lymphoma and primary mediastinal (thymic) large B-cell lymphoma serves to distinguish these tumors from other large cell lymphomas in routine clinical practice.
Article: Prolonged interferon-gamma application by subcutaneous infusion in cancer patients: differential response of serum CD14, neopterin, and monocyte HLA class I and II antigens.[show abstract] [hide abstract]
ABSTRACT: This study reports on biological response modification induced by prolonged continuous subcutaneous (s.c.) infusion of recombinant interferon-gamma (rIFN-gamma) with particular attention to changes of soluble CD14. This glycoprotein with an unknown function is derived from myeloid cells carrying membrane CD14, which is the receptor for lipopolysaccharide (LPS)-LPS-binding protein (LBP) complexes. Fifteen metastatic cancer patients received weekly escalating doses of rIFN-gamma starting at either 50 or 100 micrograms/24 h and increasing up to 400 micrograms/24 h for a median duration of 6 weeks. The maximum tolerated dose was higher (200 micrograms/24 h) with the lower (50 micrograms/24 h) starting dose. Biological activity of rIFN-gamma was evaluated by weekly measurements of CD14, neopterin, and beta 2-microglobulin concentrations in serum as well as monocyte HLA class I and II antigen expression and tumor cytotoxicity. Serum IFN-gamma concentrations increased 20-fold within 4 weeks of therapy. The levels were correlated to the mean dose (r = 0.95, p less than 0.05). Among the biological markers, two patterns were observed. First, serum CD14 concentration and expression of monocyte HLA class II antigens increased significantly during the first week, and marker expression correlated with serum IFN-gamma levels (p less than 0.05); CD14 and HLA class II antigens thereafter returned to pretreatment levels within 4 weeks of therapy despite persistently elevated serum IFN-gamma concentrations. Second, serum neopterin and beta 2-microglobulin concentrations as well as monocyte HLA class I expression also increased significantly within the first week, but remained elevated thereafter without any further dose relationship.(ABSTRACT TRUNCATED AT 250 WORDS)Journal of interferon research 05/1992; 12(2):103-11.