CD15

Synonyms: Lewis – X, LeuM1, stagespecific embryonic antigen-1 (SSEA-1)

by Assia Bassarova

Background

In humans, the terminal fucosylated lactosaminyl glycans known as Lewis-X (LeX, CD15) bear major biological significance and play key functions in cell migration, development, and immunity. Leu-M1 was first reported as reactive with the membrane-related trisaccharide fucosyl-N-acetyllactosamine on myelomonocytic cells. The gene is located on chromosome 11. CD15 is a complex cluster of cell surface glycoproteins and glycolipids having a common terminal pentasaccaharide. CD15 exists in a sialylated and an unsialylated from. Le(x) functions as an adhesion molecule capable of Ca(2+)-mediated homotypic binding. Cells with high surface expression of Le(x) therefore exhibit strong self-aggregation (based on Le(x)-Le(x) interaction) in the presence of Ca2+. The function of CD15 is not well characterized, but is most probably multifactorial.

Staining in normal tissues

CD15 is a haemopoietic differentiation antigen expressed on most terminally differentiated myeloid cells including granulocytes, eosinophils, mast cells, monocytes/macrophages, and Langerhans’ cells. Haemopoietic progenitor cells and myeloblasts do not express CD15. Only 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 T helper cells) may be positive. CD15 is also found in various epithelia such as breast (secretory epithelium), kidney (proximal tubules), lung, and gastrointestinal tract (including Paneth cells). In the brain CD15 is constantly present in astrocytes and variably in oligodendrocytes and neurons. A recent study showed that “immature” CD15 positivity in the endothelium is an important diagnostic marker of persisting villous immaturity and chronic placental dysfunction.

Staining in tumors

  • Hodgkin’s and Reed-Sternberg cells in classical Hodgkin’s disease (HD) are CD15 positive. It is important to note that malignant L&H cells, “popcorn cells” of lymphocyte predominance (LP) HD are CD15 negative.
  • Different reports has shown that 10-15% of peripheral T-cell lymphomas may express CD15 (including occasional cases of mycosis fungoides), while B-cell lymphomas are generally negative (with exception of 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 often 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. Among germ cell tumours, CD15 is detected only in mature teratoma.
  • It is suggested that sialyl-CD15 confer on the tumour cells the capacity to metastasize. In gliomas, CD15 positivity inversely correlates with the grade of malignancy.

Staining pattern

Distinct cytoplasmic granular staining in the neutrophilic granulocytes. The epithelial cells of proximal tubules of the kidney and the follicular dendritic cells in the secondary B-follicles in the tonsil / lymph nodes show distinct moderate to strong membranous staining. In classical Hodgkin’s lymphoma in addition to the membranous staining Reed-Sternberg cells show characteristic perinuclear dot-like staining.

Control tissue

Kidney, tonsil and classical Hodgkin’s lymphoma 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. All other cell types including B- and T cells must be negative. The Hodgkin’s and Reed-Sternberg cells in HD show distinct membranous and perinuclear, dot-like staining. All other cell types including B- and T cells must be negative.

Application

  • In haematopathology CD15 is important for the diagnosis of classical HD and characterization of acute myelogeneous leukaemia.
  • In the differentiation of mesothelioma vs. adenocarcinoma, CD15 can be used in the primary panel.
  • CD15 may be used for histopathological grading of gliomas and differentiating between malignant gliomas and non-neoplastic glial cells (the latter usually strongly stained).
  • In placental pathology the level of CD15 expression in the macro- and microvasculature reflects the degree of pathological placental villous immaturity.

References