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 Blood, 1 January 2008, Vol. 111, No. 1, pp. 351-358.
Prepublished online as a Blood First Edition Paper on September 26, 2007; DOI 10.1182/blood-2007-06-094151.

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NEOPLASIA

Gcet1 (centerin), a highly restricted marker for a subset of germinal center-derived lymphomas

Santiago Montes-Moreno1,2, Giovanna Roncador3, Lorena Maestre3, Nerea Martínez1, Lydia Sanchez-Verde4, Francisca I. Camacho1, Jimena Cannata1, Jorge L. Martinez-Torrecuadrada5, Yulei Shen6, Wing C. Chan6, and Miguel A. Piris1

1 Lymphoma Group, Spanish National Cancer Centre (CNIO), Madrid, Spain; 2 Department of Pathology, Hospital Universitario 12 de Octubre, Madrid, Spain; 3 Monoclonal Antibody Unit, 4 Histology and Immunohistochemistry Unit, and 5 Protein Technology Unit, CNIO, Madrid, Spain; and 6 Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha

GCET1 (germinal center B cell–expressed transcript-1) gene codes for a serpin expressed in germinal center (GC) B cells. Following the observation that follicular lymphoma cases exhibit an increased level of Gcet1 expression, compared with follicular hyperplasia, we have characterized Gcet1 protein expression in human tissues, cell lines, and a large series of lymphomas. To this end, we have performed immunohistochemical and Western blot analyses using a newly generated monoclonal antibody that is reactive in paraffin-embedded tissues. Our results demonstrate that Gcet1 is expressed exclusively by neoplasms hypothetically to be arrested at the GC stage of differentiation, including follicular lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, and a subset of diffuse large B-cell lymphoma, T-cell/histiocyte rich B-cell lymphoma, and Burkitt lymphoma. Within these tumors, Gcet-1 protein expression is restricted to a subset of GC B cells, establishing the existence of a distinct heterogeneity among normal and neoplastic GC B cells. None of the other B-cell lymphomas, that is, chronic lymphocytic leukemia, splenic marginal zone lymphoma, and mantle cell lymphoma, was Gcet1+, which underlines the potential utility of Gcet1 expression in lymphoma diagnosis. The results of RNA and protein expression should prompt further investigation into the role of Gcet1 in regulating B-cell survival.


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