CD15

CD15 is a complex cluster of cell surface glycoproteins and glycolipids having a common terminal pentasaccaharide known as the Lewisx (Lex) antigen. It is probable that the core proteins and lipids differ on the different cell types since there is a marked variability in the binding of the antibodies within and among them. CD15 exists in a sialylated and an unsialylated from. The function of CD15 is not well characterized and is most probably multifactorial. CD15 is a haemopoietic differentiation antigen expressed on most terminally differentiated myeloid cells including granulocytes, eosinophils, mast cells, monocytes/macrophages, and Langerhans' cells. CD15 is not substantially expressed on haemopoietic progenitor cells. Up to 1% of bone marrow CD34+ cells, and up to 3.8% of CD34+ cells in peripheral blood progenitor cells express CD15. The vast majority of lymphocytes are CD15 negative but activated lymphocytes (particularly T4) may be positive. CD15 is also found in various epithelia such as breast (secretory epithelium), kidney (proximal tubules), lung, and intestinal tract (including Paneth cells). In the brain CD15 is constantly present in astrocytes and variably in oligodendrocytes and neurons.

The positivity for CD15 is characteristic of Hodgkin’s cells in classical Hodgkin’s disease (HD). It is expressed in great majority of nodular sclerosis (NS), mixed cellularity (MC), lymphocyte depletion (LD) and lymphocyte rich-classical HD cases, but not in malignant cells of lymphocyte predominance (LP) HD (L&H cells, “popcorn cells”). It has been suggested that if classical HD expresses sialylated form of CD15 (sialyl-CD15), it has worse prognosis. 10-15% of peripheral T-cell lymphomas express CD15 (including occasional cases of mycosis fungoides), while B-cell lymphomas stain in an even lower proportion (usually diffuse large B-cell lymphoma). Rare cases of acute lymphoblastic leukaemia, in which myeloid antigens are often CD15 positive. Myeloid leukaemia cells express CD15 in a heterogeneous manner. CMLs are regularly CD15 positive. CD15 is expressed in a varying proportion of epithelial tumours such as adenocarcinomas (particularly from breast, lung and colon), renal cell carcinoma, apocrine carcinoma of the skin, papillary and follicular carcinoma of the thyroid, and serous carcinoma of the ovary. It is possible that sialyl-CD15 confer on the tumour cells the capacity to metastasize. Malignant mesothelioma is practically always CD15 negative (positivity has been reported in up to 6%, particularly the desmoplastic variant). In gliomas, CD15 positivity inversely correlates with the grade of malignancy. Among germ cell tumours, CD15 is detected only in mature teratoma.

In haematopathology CD15 is important for the diagnosis of classical HD and characterization of acute leukaemia. In the differentiation of mesothelioma vs. adenocarcinoma, CD15 can be used in the primary panel. Hepatocellular, gastric and colonic carcinoma and thyroid medullary carcinoma appear to have worse prognosis if positive for CD15. CD15 may be used for histopathological grading of gliomas and differentiating between malignant gliomas and non-neoplastic glial cells (the latter usually strongly stained). Detection of CD15 is frequently performed in diagnostic flow cytometry. In MDS, CD15 as well as CD10 (markers for myeloid cell maturation) are more prevalent on myeloid blasts from low-risk MDS (refractory anaemia [RA] and RA with ringed sideroblasts). A shift to a more immature phenotype with loss of CD10 and/or CD15 expression on myeloid blasts was also documented to accompany MDS progression. In acute myeloid leukaemia, the CD117(+) CD15(+) phenotype correlates significantly with complete remission achievement and with the lack of unfavourable chromosome associations.

Kidney and tonsil are recommended as positive and negative tissue controls for CD15. In the kidney the protocol must be calibrated to provide a distinct and strong predominantly membranous staining reaction in virtually all the epithelial cells of the proximal tubules and most parietal epithelial cells of Bowman’s capsule. In tonsil, follicular dendritic cells of the germinal centers must show an at least weak but distinct predominantly membranous staining reaction (the proportion of follicular dendritic cells can vary from tonsil to tonsil). The neutrophil granulocytes will show a strong cytoplasmic staining reaction. All other cell types including B- and T cells must be negative. As a supplement to kidney and tonsil, especially in the technical calibration phase of the CD15 assay, it is recommended to verify the protocol on Hodgkin lymphomas, classical subtype.