CD45 is a family of single chain transmembrane glycoproteins, 180-235 kDa, consisting of at least four isoforms which share a common large intracellular domain. Their extracellular domains are rod shaped, heavily glycosylated. The different isoforms are produced by alternative messenger RNA splicing of three exons of a single gene on chromosome 1q31-32. CD45 is expressed on cells of the human haematopoietic lineage with the exception of mature red cells. It is not detected on differentiated cells of other tissues. CD45 has intrinsic tyrosine phosphatase activity with essential for development and effector functions, playing an important role in signal transduction, inhibition or upregulation of various immunological functions. CD45 is exclusively expressed in haematolymphoid cells. Almost all haematolymphoid cells, including precursor cells and mature B- and T-lymphocytes, granulocytes, monocytes/histiocytes and interdigitating reticulum cells and follicular dendritic cells express CD45. While CD45 is strongly expressed on the lymphocyte membranes, histiocytes only exhibit a weak membrane staining. CD45 is lost in maturing erythocytes, megakaryocytes and plasma cells. The extracellular isoforms are designated ABC, AB, BC, B and O. B-lymphocytes express the high molecular weight CD45 isoform of 220 kDa, which include the isoform ABC. T-lymphocytes can express multiple isoforms. Histiocytes and granulocytes mainly express the B and O. CD45 proteins that do not comprise all of the isoforms are designated CD45R (=restricted).
CD45 is detected in the large majority of haematolymphoid neoplasms, i.e., leukaemias and malignant lymphomas. Overall, about 90% of malignant lymphomas are CD45 positive. The proportion is lower among precursor B-cell neoplasms (80% of B-ALL) and large cell anaplastic lymphomas, and only about 10% of plasmacytic neoplasms are positive. In Hodgkin lymphoma, the L&H cells in the LP-type are always positive, while Reed-Sternberg cells in classic Hodgkin lymphoma are negative or only show a faint cytoplasmic staining. CD45 is also detected in virtually all cases of mast cell neoplasms, and true histiocytic and dendritic cell neoplasms, with the possible exception of fibroblastic variants.
CD45 is an important marker in the primary tumour screening panel in order to identify haematolymphoid differentiation. Loss of CD45 in precursor B-cell neoplasms is a negative prognostic parameter.
Tonsil and liver are recommendable as positive and negative tissue controls. In tonsil, all lymphocytes (B- and T-cells) and histiocytes must display a strong distinct membranous staining reaction. Squamous epithelial cells should be negative. In liver, the Kupffer cells should show a weak to moderate staining reaction whereas hepatocytes must be negative. Scattered lymphocytes can be seen in the liver and must display strong, distinct membranous staining reaction.
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