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


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.


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.
Roncador
Giovanna
G
Monoclonal Antibodies Unit, Biotechnology Program,Spanish National Cancer Centre, Madrid, Spain. david.mason@ndcls.ox.ac.uk
García Verdes-Montenegro
José-Francisco
JF
Tedoldi
Sara
S
Paterson
Jennifer C
JC
Klapper
Wolfram
W
Ballabio
Erica
E
Maestre
Lorena
L
Pileri
Stefano
S
Hansmann
Martin-Leo
ML
Piris
Miguel A
MA
Mason
David Y
DY
Marafioti
Teresa
T
D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis*; D015703:Antigens, CD / Q000032:analysis*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D051017:Apoptosis Regulatory Proteins / Q000032:analysis*; D018858:Germinal Center / Q000473:pathology*; D006689:Hodgkin Disease / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007119:Immunoblastic Lymphadenopathy / Q000378:metabolism / Q000473:pathology*; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis*; D016246:Lymphocytes, Tumor-Infiltrating / Q000737:chemistry / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000737:chemistry / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000378:metabolism / Q000473:pathology*; D009363:Neoplasm Proteins / Q000032:analysis*; D014066:Palatine Tonsil / Q000473:pathology; D061026:Programmed Cell Death 1 Receptor; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000737:chemistry* / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein