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Published on: April 13, 2015
Intracellular signalling molecules as immunohistochemical markers of normal and neoplastic human leucocytes in
Michela Pozzobon1, Teresa Marafioti, Martin-Leo Hansmann
1Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, UK.
Insights
Intracellular signaling molecules like SLP-76 and Lyn can serve as immunohistological markers for human white blood cells. This study identifies specific markers for T cells and B cells, aiding in the diagnosis of lymphomas.
Area of Science:
- Immunology
- Cell Biology
- Hematology
Background:
- Intracellular signal transduction molecules are crucial for leukocyte function.
- Identifying reliable immunohistological markers for human leukocytes in routine tissue sections is essential for diagnostics.
Purpose of the Study:
- To investigate the utility of intracellular signal transduction molecules as immunohistological markers for normal and neoplastic human leukocytes.
- To determine the selective labeling patterns of specific signaling molecules in different leukocyte subsets.
Main Methods:
- Immunohistochemical staining of routine human tissue sections.
- Utilized antibodies against eight intracellular signal transduction molecules: SLP-76, BLNK, Lyn, Fyn, Syk, Hck, PLC-gamma1, and PLC-gamma2.
Main Results:
- Selective labeling of T cells by SLP-76 and PLC-gamma1.
- Selective labeling of B cells by BLNK, Lyn, Fyn, Syk, and PLC-gamma2.
- Identified markers for thymocyte precursors, megakaryocytes, myeloid cells, macrophages, and arterial endothelium.
- Demonstrated presence of T cell markers in most T-cell lymphomas and B cell markers in most B-cell non-Hodgkin's lymphomas.
Conclusions:
- Intracellular signaling molecules can be effectively detected in routine biopsies.
- These markers offer new possibilities for studying normal and neoplastic human white cells in diagnostic settings.
- Specific signaling molecules show promise as diagnostic markers for lymphoid malignancies.
Abstract:
We have investigated whether intracellular signal transduction molecules can be used as immunohistological markers of normal and neoplastic human leucocytes in routine tissue sections. We obtained selective labelling of white cells for eight such molecules (the 'linker' molecules SLP-76 and BLNK, the Src family kinases Lyn, Fyn, Syk and Hck, and the phospholipases PLC-gamma1 and PLC-gamma2). Antibodies to SLP-76 and PLC-gamma1 selectively labelled T cells, and antibodies to BLNK, Lyn, Fyn, Syk and PLC-gamma2 labelled B cells (although Fyn immunostaining was restricted to mantle zone B cells). Antibodies to the Syk and Hck kinases labelled probable thymocyte precursors at the periphery of the thymic cortex. In addition to lymphoid cells, several other leucocyte types were immunostained (e.g. SLP-76, Lyn, Syk and Hck were found in megakaryocytes, myeloid cells and/or macrophages, and PLC-gamma2 was detected in arterial endothelium). SLP-76 and PLC-gamma1 were found in most T-cell lymphomas studied, and some B-cell lymphomas were also positive for PLC-gamma1 (e.g. diffuse large cell and Burkitt's lymphoma). The five B cell-associated markers were found in most B-cell non-Hodgkin's lymphomas, although some diffuse large B-cell lymphomas were negative (e.g. for Lyn) and anti-Fyn tended not to stain small B-cell neoplasms. The observation that a range of leucocyte signalling molecules can be detected in routine biopsies offers new possibilities for studying normal and neoplastic human white cells in diagnostic tissue samples.
