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Expression of two markers of germinal center T cells (SAP and PD-1) in angioimmunoblastic T-cell lymphoma

From the Monoclonal Antibodies Unit, Biotechnology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain (GR, J-FGV-M, LM); Leukaemia Research Fund (LRF) Immunodiagnostics Unit, Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Oxford, UK (ST, JCP, EB, DYM, TM); Department of Hematopathology and Lymph Node Registry Kiel, Schleswig-Holstein University Hospitals, Kiel, Germany (WK); Chair of Pathology and Unit of Hematopathology, "L&A Seragnoli" Institute of Hematology, University of Bologna, Bologna, Italy (SP); Senckenberg Pathology Institute, Johann Wolfgang Goethe-University Clinic Frankfurt am Main, Frankfurt am Main, Germany (M-LH); Molecular Pathology Programme, Spanish National Cancer Centre (CNIO), Madrid, Spain (MAP)

Correspondence: David Y. Mason, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, OX3 9DU, UK. E-mail: david.mason{at}ndcls.ox.ac.uk

Background and Objectives: In the present paper we report that SAP, an intracytoplasmic molecule that is involved in cell signaling, is an immunohistologic marker for germinal center T cells in paraffin-embedded tissue. We document its expression, and also that of PD-1 (another recently described marker of germinal center T cells to which a new antibody has been raised), in normal and neoplastic lymphoid tissue to evaluate the suggestion that helper T cells within the germinal centers of human lymphoid tissue are the cell of origin of angioimmunoblastic T-cell lymphoma (AITL), and to assess the diagnostic value of these two markers.

Design and Methods: Expression of SAP and PD-1 was investigated by immunohistochemistry in paraffin-embedded tissue sections and in cell lines. Western blotting was performed on cell lines, and antibody specificity was confirmed by immunostaining of transfected cells.

Results: Screening on more than 500 lymphoma biopsies showed that 95% (40/42) of cases of AITL expressed at least one of these markers. SAP was also expressed on many cases (15/21) of acute T lymphoblastic leukemia, in keeping with its presence in cortical thymocytes. However, PD-1 and SAP were also found in a minority of cases of peripheral T-cell lymphoma other than AITL, in contrast to a report that the former marker is specific for AITL. This observation raises the possibility that such non-angioimmunoblastic cases may be related to germinal center helper T cells.

Interpretation and Conclusions: These two markers provide additional evidence that AITL arises from germinal center T cells. They may also prove of value in the diagnosis of this disease since a negative reaction was rarely observed in this disorder.

Key words: lymphoma, AITL, germinal center T cells, immunohistochemistry, western blotting.