Expression of serine 194-phosphorylated Fas-associated death domain protein correlates with proliferation in B-cell non-Hodgkin lymphomas.

Abstract

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.

• Authors: Elias Drakos, Vasiliki Leventaki, Vasileios Atsaves, Ellen J Schlette, Pei Lin, Francisco Vega, Roberto N Miranda, Francois-Xavier Claret, L Jeffrey Medeiros, George Z Rassidakis
• Journal: Human pathology (Hum Pathol) Vol. 42 Issue 8 Pg. 1117-24 (Aug 2011) ISSN: 1532-8392 [Electronic] United States
• PMID: 21315423 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor
• FADD protein, human
• Fas-Associated Death Domain Protein
• Ki-67 Antigen
• Serine

Topics

• Biomarkers, Tumor (metabolism)
• Cell Count
• Cell Cycle (physiology)
• Cell Line, Tumor
• Cell Nucleus (metabolism, pathology)
• Cell Proliferation
• Fas-Associated Death Domain Protein (metabolism)
• Germinal Center (metabolism, pathology)
• Humans
• Immunohistochemistry
• Ki-67 Antigen (metabolism)
• Lymph Nodes (metabolism, pathology)
• Lymphadenitis (metabolism, pathology)
• Lymphoma, B-Cell (metabolism, pathology)
• Phosphorylation
• Serine (metabolism)
• Tonsillitis (metabolism, pathology)