CD68

Characteristics

Anti-CD68-antibodies detect a glycoprotein with a molecular weight of approximately 110 kD, localized in the cytoplasm, often with relation to lysosomes. Positive staining is seen in different types of macrophages of monocyte lineage and antibodies also reacts with myeloid precursor cells in the bone marrow. Positivity is seen in Kupffer cells and histiocytes in normal lymphoid tissue (Fig. 1), but also mast cells and microglia. Thus, there are reasons to believe that the antigen may be expressed in a wider range of cells than cells of pure myeloid/monocytic/histiocytic origin and differentiation.

Neoplasms

Fibrous-histiocytic tumours such as juvenile xanthogranuloma (Fig. 2) and Langerhans cell histiocytosis, subtypes of myeloid leukaemia (depending on the Ab used), some epithelial neoplasms, epithelioid cells of some malignant melanomas.

Application

Anti-CD68-antibodies are of value for the diagnosis of fibrous-histiocytic tumours, histiocytosis and other conditions with an abundance of histiocytes. Immunohistochemical detection of CD68-positivity may also be of some importance in the diagnosis of glial changes and proliferations, malignant melanoma and myeloid leukaemia. As regards the latter, CD68 (clone PG-M1) may be applicable in identifying a monocytic differentiation in a pattern corresponding that of CD14.
 

Visualization

A number of different monoclonal antibodies to CD 68 have been used and are commercially available. The most widely used clones have been KP-1, PG-M1, Ki-M6, Ki-M7, and EBM11. The reactivity and specificity may be somewhat varying for the different clones. It appears that MG-M1 gives a better signal-to-noise ratio than KP1 (see Assessments) and stains a narrower spectrum of cells. For example, in acute myeloid leukaemia, KP1 also stains non-monocytic subtypes, which are not stained with PG-M1 or CD14. HIER is mandatory, an alkaline buffer should be preferred, e.g., Tris-EDTA pH9. Some companies recommend proteolytic pretreatment. However, proteolysis hampers the staining result and should be avoided.
Control tissue: Normal liver, appendix and brain are appropriate tissues. The hepatic Kupffer cells and the macrophages of the germinal centres and lamina propria must be strongly stained. A faint staining of some T-cells may be discerned. If mAb KP1 is used, a faint staining of enterocytes is seen as well. In the brain the microglia must be strongly stained without any background staining.

Assessments

Run 11 2004
Run 26 2009

Selected references

Chang CC, Eshoa C, Kampalath B, Shidham VB, Perkins S. Immunophenotypic profile of myeloid cells in granulocytic sarcoma by immunohistochemistry. Correlation with blast differentiation in bone marrow.
Am J Clin Pathol. 2000 Nov;114(5):807-11.

Falini B, Flenghi L, Pileri S, Gambacorta M, Bigerna B, Durkop H, Eitelbach F, Thiele J, Pacini R, Cavaliere A, et al. PG-M1: a new monoclonal antibody directed against a fixative-resistant epitope on the macrophage-restricted form of the CD68 molecule. Am J Pathol. 1993 May;142(5):1359-72.

Groisman GM, Amar M, Schafer I. The histiocytic marker PG-M1 is helpful in differentiating histiocytes and
histiocytic tumors from melanomas. Appl Immunohistochem Mol Morphol. 2002 Sep;10(3):205-9.

Groisman GM, Schafer I, Amar M, Sabo E.  Expression of the histiocytic marker PG-M1 in granuloma annulare and rheumatoid nodules of the skin. J Cutan Pathol. 2002 Nov;29(10):590-5.

Manaloor EJ, Neiman RS, Heilman DK, Albitar M, Casey T, Vattuone T, Kotylo
P, Orazi A. Immunohistochemistry can be used to subtype acute myeloid leukemia in routinely processed bone marrow biopsy specimens. Comparison with flow cytometry. Am J Clin Pathol. 2000 Jun;113(6):814-22.

Nascimento AG. A clinicopathologic and immunohistochemical comparative study of cutaneous and intramuscular forms of juvenile xanthogranuloma. Am J Surg Pathol. 1997 Jun;21(6):645-52.