Expression of serine 194-phosphorylated Fas-associated death domain protein correlates with proliferation in B-cell non-Hodgkin lymphomas. Hum Pathol 2011 Aug;42(8):1117-24
Date
02/15/2011Pubmed ID
21315423Pubmed Central ID
PMC4089890DOI
10.1016/j.humpath.2010.11.002Scopus ID
2-s2.0-79960429920 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
Fas-associated death domain protein is a key component of the extrinsic apoptotic pathway. In addition, in animal models, Fas-associated death domain protein phosphorylation at serine 194 has been shown to affect cell proliferation, especially in T lymphocytes. The importance of Fas-associated death domain protein phosphorylation at serine 194 for the proliferation of B lymphocytes, however, is uncertain. Here we show in reactive lymph nodes that serine 194 phosphorylated Fas-associated death domain protein is expressed predominantly in the dark (proliferative) zone of germinal centers. In B-cell non-Hodgkin lymphoma cell lines, serine 194 phosphorylated Fas-associated death domain protein levels are substantially higher in highly proliferating cells and lower in serum-starved cells. We also used immunohistochemical analysis to assess Fas-associated death domain protein phosphorylation at serine 194 expression in 122 B-cell non-Hodgkin-type lymphomas. The mean percentage of serine 194 phosphorylated Fas-associated death domain protein positive tumor cells was 81% in Burkitt lymphoma, 41% in diffuse large B-cell lymphoma, 18% in follicular lymphoma, 18% in plasma cell myeloma, 12% in extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, 11% in mantle cell lymphoma, and 2% in chronic lymphocytic leukemia/small lymphocytic lymphoma (P < .0001, Kruskal-Wallis test). Furthermore, in chronic lymphocytic leukemia/small lymphocytic lymphoma, serine 194 phosphorylated Fas-associated death domain protein was detected predominantly in proliferation centers. In the entire study group, the percentage of cells positive for serine 194 phosphorylated Fas-associated death domain protein correlated significantly with the proliferation index Ki-67 (Spearman R = 0.9, P < .0001). These data provide evidence that serine 194 phosphorylated Fas-associated death domain protein is involved in the proliferation of normal and neoplastic B cells and has features of a novel proliferation marker.
Author List
Drakos E, Leventaki V, Atsaves V, Schlette EJ, Lin P, Vega F, Miranda RN, Claret FX, Medeiros LJ, Rassidakis GZMESH terms used to index this publication - Major topics in bold
Biomarkers, TumorCell Count
Cell Cycle
Cell Line, Tumor
Cell Nucleus
Cell Proliferation
Fas-Associated Death Domain Protein
Germinal Center
Humans
Immunohistochemistry
Ki-67 Antigen
Lymph Nodes
Lymphadenitis
Lymphoma, B-Cell
Phosphorylation
Serine
Tonsillitis