CD34

Characteristics
CD34 (also named myeloid progenitor cell antigen) is a heavily glycosylated type I transmembrane protein, 110 kDa. There are two forms of the CD34 protein, resulting from alternative splicing. The functions of CD34 is largely unknown, but recent evidence suggests a role for CD34 in cell adhesion and inhibition of hematopoiesis. It is suggested that CD34 is a signalling molecule involved in maintenance of a phenotypically plastic state in undifferentiated cells. CD34 protein (using mAb QBEND10) is detected in bone marrow precursor cells including hematogones, where it might act as a ligand for lectins in the cells of the bone marrow stroma. The finding of intracytoplasmic and Golgi-type positivity in bone marrow sections is very frequently seen along with membranous-type positivity. However, many of the cells have no membrane positivity at all (this is hardly surprising because there are intracellular stores of CD34 protein that can be quickly translocated to the plasma membrane in response to extracellular signals, which enable rapid upregulation of CD34 surface expression in normal human bone marrow cells). CD34 disappears from all haematological cell lines during maturation. Megakaryocytes are variably positive for CD34. CD34 is found in most endothelia, expressed on the luminal surface and membrane processes interdigitating between endothelial cells, but is absent from large veins and arteries. CD34 is also absent from sinuses in the placenta and spleen. Lymphatics are generally weakly stained. CD34 is furthermore expressed in fibroblast-like dendritic cells in, e.g., portal tracts of the liver, Peyer's patches, and in healing wounds. In smooth muscle cells, a variable CD34 staining is found.
Neoplasms
CD34 is detected in myeloid blasts in myelodysplastic syndrome and acute myeloid leukaemia in most cases as well as lymphoblasts in most cases of B-acute lymphoblastic leukaemia. Mature B- and T-cell lymphomas and leukaemias are CD34 negative. The majority of vascular tumours, including haemangiosarcoma and Kaposi sarcoma are CD34 positive, the protein frequently being expressed in abluminal processes. However, only about 30% of the lymphangiomas are CD34 positive. CD34 positivity is seen in most cases of dermatofibrosarcoma protuberans, solitary fibrous tumor, lipoma (particularly spindle cell lipoma) and liposarcoma, gastrointestinal stromal tumor (strong positivity in about 80% of the cases, which are also CD117 positive), and a varying proportion of meningioma. Moderate expression is seen in cutaneous leiomyoma, while weak expression is present in uterine and soft tissue smooth muscle tumours. Some cases of myofibroblastoma have revealed CD34 positivity. Schwannoma is CD34 positive mainly in Antoni B areas. Neurofibroma and neurofibrosarcoma may also stain. About 50% of epitheloid sarcomas show strong focal or generalized staining for this antigen. Some synovial sarcomas may show focal staining. Fibrous histiocytoma is CD34 negative. CD34 is expressed only exceptionally in carcinomas (kidney, thyroid gland) and clear cell sarcoma/melanoma.
Application
In a panel, CD34 staining is useful for the classification of myeloid and lymphoid neoplasms as well as spindle cell neoplasms (particularly identification of gastrointestinal stromal tumour and haemangiosarcoma).
Controls
Liver and appendix is recommended as positive and negative tissue controls for CD34. In liver the protocol must be calibrated to provide a moderate to strong predominately membranous staining reaction of endothelial cells in the portal vessels, but also of the periportal sinusoidal endothelial cells serving as “low expressors” for an optimal calibrated assay for CD34. No staining reaction must be seen in liver cells. As a supplement to liver, appendix can be used. All endothelial cells and, in particular endothelial cells lining the small vessels in lamina propria, Cajal cells in muscularis propria and stromal fibroblast-like cells must be stained as strongly as possible without any staining reaction of smooth muscle cells and epithelial cells.
Selected references
Baumheter S, Singer MS, Henzel W, et al. Binding of L-selectin to the vascular sialomucin CD34. Science. 1993;262:436-438. Baur AS, Meugé-Moraw C, Schmidt P-M, et al. CD34/QBEND10 immunostaining in bone marrow biopsies: an additional parameter for the diagnosis and classification of myelodysplasic syndromes. Eur J Haematol. 2000;64:71-79. Fackler MJ, Civin CI, May WS. Up-regulation of surface CD34 is associated with protein kinase C-mediated hyperphosphorylation of CD34. J Biol Chem. 1992;267:17540-6. Fackler M, Krause D, Smith O, et al. Full-length but not truncated CD34 inhibits hematopoietic cell differentiation of M1 cells. Blood. 1995;85:3040. Fina L, Molgaard HV, Robertson D, et al. Expression of the CD34 gene in vascular endothelial cells. Blood. 1990;75:2417. Horny H-P, Wehrmann M, Schlicker HUH, et al. QBEND10 for the diagnosis of myelodysplastic syndrome in routinely processed bone marrow biopsy specimens. J Clin Pathol. 1995;48:291-294. Krause DS, Fackler MJ, Civin CI, et al. CD34: Structure, biology, and clinical utility. Blood. 1996;87:1-13. Longacre TA, Foucar K, Crago S, et al. Hematogones: a multiparameter analysis of bone marrow precursor cells. Blood. 1989;73:543-552. Natkunam Y, Rouse RV, Zhu S, Fisher C, van De Rijn M. Immunoblot analysis of CD34 expression in histologically diverse neoplasms. Am J Pathol. 2000 Jan;156(1):21-7. Rimsza LM, Viswanatha DS, Winter SS, et al. The presence of CD34+ cell clusters predicts impending relapse in children with acute lymphoblastic leukemia receiving maintenance chemotherapy. Am J Clin Pathol. 1998;110:313-320. Silverman JS, Tamsen A. Fibrohistiocytic differentiation in subcutaneous fatty tumors. Study of spindle cell, pleomorphic, myxoid, and atypical lipoma and dedifferentiated liposarcoma cases composed in part of CD34+ fibroblasts and FXIIIa+ histiocytes. J Cutan Pathol 1997 24:484 Silverman JS, Tamsen A. Mammary fibroadenoma and some phyllodes tumour stroma are composed of CD34+ fibroblasts and factor XIIIa+ dendrophages. Histopathology 1996 29:411. Toth B, Wehrmann M, Kaiserling E, et al. Immunophenotyping of acute lymphoblasic leukaemia in routinely processed bone marrow biopsy specimens. J Clin Pathol. 1999;52:688-692. van de Rijn M, Hendrickson MR, Rouse RV. CD34 expression by gastrointestinal tract stromal tumors. Hum Pathol. 1994 Aug;25(8):766-71. van de Rijn M, Lombard CM, Rouse RV. Expression of CD34 by solitary fibrous tumors of the pleura, mediastinum, and lung. Am J Surg Pathol. 1994 Aug;18(8):814-20.
20.04.16 - ET/MV/LE