by Jan Klos
Background
The target is a family of acidic glycoproteins of not fully understood function located in lysosomes, phagolysosomes and neutrophil primary granules. The murine monoclonal antibodies KP1 and PGM1 are in wide use. Both are sensitive antibodies with some differences in the spectrum of reactivity. CD68 may be not considered a selective macrophage marker, but rather a lysosomal protein that is enriched in macrophages
Staining in normal cells with KP1 antibody is reported in monocytes and macrophages in the different tissues, osteoclasts, myeloid precursor cells as well as mature myeloid cells. Spectrum of staining with PGM1 antibody is similar except negative results in granulocytes and myeloid precursor cells. Additionally PGM1 antibody stains also mast cells and synovial cells.
Staining in tumors: Since majority of cases of acute myeloid leukemia (AML) is stained with KP1 clone (types M1-M5) while clone PGM1 stains only cases with myelomonocytic and monocytic differentiation (types M4-M5) so the results can be used for subtyping of acute leukemias. Staining is also present in malignant histiocytosis, histiocytic lymphoma, granulocytic sarcoma, mast cell proliferations, chronic myeloid and myelomonocytic leukemias. Majority of cases Langerhans cell proliferations, Gaucher cells, interdigitating reticulum cell sarcoma, follicular dendritic cell sarcoma, synovial sarcoma, granular cell tumors as well as macrophage proliferations are also positive. Some B-lymphocyte proliferations like small lymphocytic lymphomas, MALT lymphomas and hairy cell leukemia are positive in about 70%. A number of benign and malignant tumors of non-epithelial and some of epithelial origin with lysosome rich tumor cells as well as infiltrating tumor macrophages is also labelled. CD68 may be considered a lysosomal protein that is enriched mostly in macrophages but not a specific macrophage marker.
Staining pattern is granular cytoplasmic resembling distribution of lysosomes in the cells.
Application
As a part of the panel in diagnosis and subtyping of tumors. One of the potential pitfalls may be the high percentage of reactivity in tumors (mesenchymal, epithelial and even melanocytic) of non monocyte/macrophage lineage of differentiation.
Selected references:
- Chetty R., Cooper K., Gown A.M. Leong`s manual of Diagnostic Antibodies for Immunohistology. ed. Cambridge University Press; 3rd edition 2016. ISBN-13 : 978-1107077782
- Gottfried E., Kunz‐Schughart L.A., Weber A. et al. Expression of CD68 in Non‐Myeloid Cell Types. Scand J Immunol 2008 May;67(5):453-63. doi: 10.1111/j.1365-3083.2008.02091.x.
- https://app.immunoquery.com/engine/abpanel?abs=CD68
- Lau S.K., Chu P.G., Weiss L.M. CD163: a specific marker of macrophages in paraffin-embedded tissue samples. Am J Clin Pathol 2004;122:794-801, 794 DOI: 10.1309/QHD6YFN81KQXUUH6 PMID: 15491976
- Torlakovic E.E. Naresh K. Brunning R.D. Bone marrow Immunohistochemistry. ed. American Society for Clinical Pathology Press 2009. ISBN 0891895728, 9780891895725