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(American Journal of Pathology. 1999;154:1037-1046.)
© 1999 American Society for Investigative Pathology


Technical Advance

Linker for Activation of T Cells (LAT), a Novel Immunohistochemical Marker for T Cells, NK Cells, Mast Cells, and Megakaryocytes

Evaluation in Normal and Pathological Conditions

Fabio Facchetti* , John K. C. Chan§ , Weiguo Zhang|| , Andrea Tironi* , Marco Chilosi¶ , Silvia Parolini{dagger} , Luigi D. Notarangelo{ddagger} and Lawrence E. Samelson||

From the Departments of Pathology,* Biomedical Sciences and Biotechnology,{dagger} and Pediatrics,{ddagger} University of Brescia, Brescia, Italy; the Queen Elizabeth Hospital,§ Hong Kong, China; the University of Verona, Verona, Italy, and the Section on Lymphocyte Signaling,|| Cell Biology and Metabolism Branch, National Institutes of Health, Bethesda, Maryland

LAT (linker for activation of T cells) is an integral membrane protein of 36–38 kd that plays an important role in T cell activation. Using a rabbit polyclonal antibody generated against the cytosolic portion of LAT, we investigated the immunohistochemical expression of LAT in normal and pathological hematolymphoid tissues. LAT reacts with human T cells in paraffin sections, including decalcified bone marrow trephines. LAT appears early in T cells at the thymocyte stage and before TdT expression in embryos, and is expressed in peripheral lymphoid tissues, without restriction to any T cell subpopulations. In addition to T cells, natural killer (NK) cells (evaluated with flow cytometry), megakaryocytes and mast cells are also LAT-positive, whereas B cells and other myeloid and monocytic derived cells are negative. Tested on a total of 264 paraffin-embedded tissue biopsies, LAT reacted with the great majority (96.8%) of T/NK-cell neoplasms, covering the full range of T cell maturation. Although antibodies to both LAT and CD3 had a similarly high sensitivity in the staining of T/NK-cell lymphomas, when used in conjunction, they successfully identified a higher number of cases (98.4%). Atypical megakaryocytes from different hematological disorders, as well as mast cells in mastocytosis were also LAT-positive, but all neoplasms of B cell origin, Hodgkin's lymphomas, and several nonlymphoid malignancies were negative. These data indicate that the anti-LAT antibody may be of value to diagnostic histopathologists for the identification of T cell neoplasms.





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