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 (Fig. 1A), 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) (Fig. 1B), 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) (Fig. 2A). 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 (Fig. 2B), lung (Fig. 2C) 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)(Fig. 2D).
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.
There are about 90 mAb clones assigned
to CD15 and eight alternate names for CD15.
Most of anti-CD15 mAbs, such as MMA, LeuM1 and
are IgM Abs and do not react with the sialylated form (CD15s or
sialyl-CD15). The mAbs FH6 and CSLEX1
are directed against sialylated CD15. The binding of each mAb can be markedly increased by
exposure of the cell surface to neuraminidase (muramidase), presumably by desialylating
CD15, particularly in acute myeloid leukaemia.
Fixation is important. It is easier to detect CD15 in B5-fixed tissues than in formalin-fixed tissues. Since this is just the opposite for CD30, it is important to try to sample lymph node tissue for fixation in both fixatives for optimal work up of HD.
Arber D, Weiss L. CD15: a review. Appl Immunohistochem 1993;1:17-30.
Bahia DM, Yamamoto M, Chauffaille Mde L, Kimura EY, Bordin JO, Filgueiras MA, Kerbauy J. Aberrant phenotypes in acute myeloid leukemia: a high frequency and its clinical significance. Haematologica. 2001 Aug;86(8):801-6.
Brooks SA, Leathem AJ. Expression of the CD15 antigen (Lewis x) in breast cancer. Histochemical Journal, 1995;27(9):689-93.
Charalambous C, Singh N, Isaacson PG. Immunohistochemical analysis of Hodgkin's disease using microwave heating. Journal of Clinical Pathology, 1993;46(12):1085-8.
Gocht A, Struckhoff G, Lhler J. CD15-containing
glycoconjugates in the central nervous system. Histol Histopathol.
Mayer B, Funke I, Johnson JP. High expression of a Lewis(x)-related epitope in gastric carcinomas indicates metastatic potential and poor prognosis. Gastroenterology, 1996;111(6):1433-46.
Nakamori S, Kameyama M, Imaoka S, Furukawa H, Ishikawa O, Sasaki Y, Kabuto T, Iwanaga T, Matsushita Y, Irimura T. Increased expression of sialyl Lewisx antigen correlates with poor survival in patients with colorectal carcinoma: clinicopathological and immunohistochemical study. Cancer Research, 1993;53(15):3632-7.
Ogata K, Nakamura K, Yokose N, Tamura H, Tachibana M, Taniguchi O, Iwakiri R, Hayashi T, Sakamaki H, Murai Y, Tohyama K, Tomoyasu S, Nonaka Y, Mori M, Dan K, Yoshida Y. Clinical significance of phenotypic features of blasts in patients with myelodysplastic syndrome. Blood. 2002 Dec 1;100(12):3887-96. Epub 2002 Jul 18.
Ohtani H, Fukushi Y, Orikasa S, Nagura H. Qualitative difference of subcellular localization of tumor-associated carbohydrate (Le(x)) antigens in renal cell carcinoma and normal kidney. Journal of Histochemistry and Cytochemistry, 1991;39:479-84.
Reifenberger G, Sieth P, Niederhaus M, Wechsler W. Expression of CD15 in tumours of the nervous system. Histochemical Journal, 1992;24(11):890-901.
Stetler-Stevenson M, Arthur DC, Jabbour N, Xie XY, Molldrem J, Barrett AJ, Venzon D, Rick ME. Diagnostic utility of flow cytometric immunophenotyping in myelodysplastic syndrome. Blood. 2001 Aug 15; 98(4): 979-87.
Valente AM, Taatjes DJ, Mount SL. Comparison of the pattern of expression of Leu-M1 antigen in adenocarcinomas, neutrophils and Hodgkin's disease by immunoelectron microscopy. Histochemistry and Cell Biology, 1995;103:181-6.