CD 34

Becton Dickinson (MY10), Biodesign (QBEND/10), Biogenex (QBEND/10), Cymbus Bioscience, Dako (BIRMA-K3), Gen Trak, Immunotech (QBEND/10, IMMU133.3), Oncogene, PerSeptive, RDI (9BI-3c5, ICH3), Selinus (B1-3C5), Seralab (BI-3C5) and Serotec (QBEND/10).

Antibodies are immunoreactive in fixed tissue and staining is significantly enhanced by HIER.

The CD 34 antigen is a 110 kD, heavily glycosylated transmembrane protein of generally unknown function. Some evidence suggests that CD 34 might play a role in cell adhesion with the highly glycosylated molecule allowing it to act as a ligand for lectins. In this way, CD 34+ hematopoietic precursors might bind to lectin-expressing cells of the bone marrow stroma. The CD 34 antigen was originally defined by monoclonal antibody MY10 raised against the human myeloid leukemia cell line KG1a. The gene for CD 34 has been localized to chromosome 1 in the region of 1q32 and the DNA sequence demonstrates no homology with any previously known human genes (Baum et al, 1992; Greaves et al, 1992).
The CD 34 antigen is present on ~ 1% of normal bone marrow mononuclear cells including hematopoietic precursors/stem cells. Thus, antibodies to CD 34 can be used to purify the CD 34+ stem cell population from CD 34- malignant cells. The CD 34+ bone marrow population contains not only hematopoietic stem cells but also more mature lineage-committed precursor cells for the erythroid, myeloid and lymphoid lineages. Included among these CD 34+ cells are stromal cells necessary for the appropriate bone marrow environment for hematopoiesis (Baum et al, 1992).
The demonstration of CD 34 on immature leukemias and vascular neoplasms has been the main contribution to its diagnostic utility. Besides bone marrow stem cells and normal endothelial cells, the antigen is found on cells in the splenic marginal zone and dendritic interstitial cells around vessels, nerves, hair follicles, muscle bundles and sweat glands in a variety of tissues and organs. CD 34+ cells appear in the peripheral blood after treatment with chemotherapy or cytokines. In blood vessel endothelium the antigen may be absent from large veins and arteries and from sinuses in the placenta and spleen. It is expressed on the luminal surface and membrane processes that interdigitate between endothelial cells. In new vessels such as in tumors, the location of the antigen is altered and it is found on the abluminal microprocesses of such vessels (Van De Rijn & Rouse, 1994).
Among the hematopoietic neoplasms, CD 34 is seen in the immature leukemias such as acute lymphoblastic leukemia of both T-and B-cell lineage and acute myeloblastic leukemia. In myelodysplastic syndromes the expression of CD 34 was predictive of transformation and poor survival outcome. There is some confusion over the value of CD 34 as a prognostic parameter in the leukemias. Some studies have suggested that its expression is a poor prognosticator in AML whereas it is a marker of good prognosis in childhood ALL, probably those restricted to B-cell lineage all these studies being performed with flow cytometry analysis (Van De Rijn & Rouse, 1994).

The expression of CD 34 is retained in malignant endothelial cells so that it is a good marker for vascular tumors (Appendices 1.22 and 1.23). The endothelial cells of both vascular and lymphatic vessels express the antigen (Ramani et al, 1990; Suthipintawong et al, 1995). There is variable staining for CD 34 in smooth muscle cells and their tumors. Antibodies to CD 34 label gastrointestinal stromal tumors (GIST) very strongly (Appendix 1.25). Epithelioid smooth muscle tumors stain less frequently but the marker may serve as a useful discriminator from epithelial tumors which are generally negative for CD 34 (Sirgi et al, 1993). The antigen is displayed by nerve sheath tumors although in some series both neurofibromas and schwannomas failed to stain. In the latter, staining may be mainly in the Antoni B areas. While the staining in malignant nerve sheath tumors is largely negative, some series report a high frequency of reactivity, suggesting that CD 34 may be a useful inclusion in the diagnostic panel for such tumors as S100 and CD57 are negative in such tumors (Weiss & Nickoloff, 1993). Epithelioid sarcoma and hemangiopericytoma show staining for CD 34 and the marker is invariably found in solitary fibrous tumors and dermatofibrosarcoma protuberans, two tumors which are generally recognized from their histologic mimics by the absence of specific markers (Kutzner, 1993; Westra et al, 1994). Recently, CD 34 was also demonstrated in four of 12 cases of angiomyofibroblastomas (Neilsen et al, 1996). Interestingly, reactivity for CD 34 was found in giant cell fibroblastomas and one Bednar tumor, supporting the relationship of such tumors to dermatofibrosarcoma protuberans. CD 34 is also a useful marker for early myeloid cells and hence stains granulocytic sarcoma.

Much of the earlier controversy concerning the staining of CD 34 in spindle cell tumors was due to the sensitivity of the staining technique. CD 34 staining is greatly enhanced by heat-induced epitope retrieval, especially microwave-induced techniques.

•Baum CM, Weissman IL, Tsukamoto AS et al 1992. Isolation of a candidate human hematopoietic stem-cell population. Proceedings of the National Academy of Science USA 89: 2804-2808.

•Greaves MF, Brown J, Molgaard HV et al 1992. Molecular features of CD 34: a hematopoietic progenitor cell-associated molecule. Leukemia 1:31-36.

•Kutzner H 1993. Expression of the human progenitor cell antigen CD 34 (HPCA-1) distinguished dermatofibrosarcoma protuberans from fibrous histiocytoma in formalin-fixed, paraffin-embedded tissue. Journal of the American Academy of Dermatology 28: 613-617.

•Neilsen GP, Rosenberg AE, Young RH et al 1996. Angiomyofibroblastoma of the vulva and vagina. Modern Pathology 9: 284-291.

•Ramani P, Bradley NJ, Fletcher CMD 1990. QBEND/10, a new monoclonal antibody to endothelium: assessment of its diagnostic utility in paraffin sections. Histopathology 17: 237-242.

•Sirgi KE, Wick MR, Swanson PE 1993. B72.3 and CD 34 immunoreactivity in malignant epithelioid soft tissue tumors: adjuncts in the recognition of endothelial neoplasms. American Journal of Surgical Pathology 17: 179-185.

•Suthipintawong C, Leong AS-Y, Vinyuvat S 1995. A comparative study of immunomarkers for lymphangiomas and hemangiomas. Applied Immunohistochemistry 3: 239-244.

•Van De Rijn M, Rouse RV 1994. CD 34. A review. Applied Immunohistochemistry 1994; 2: 71-80

•Weiss SW, Nickoloff BJ 1993. CD 34 is expressed by a distinctive population in peripheral nerve, nerve sheath tumors and related lesions. American Journal of Surgical Pathology 17: 1039-1045

•Westra WH, Gerald WL, Rosai J 1994. Solitary fibrous tumor. Consistent CD 34 immunoreactivity and occurrence in the orbit. American Journal of Surgical Pathology 18: 992-998. occurrence in the orbit. American Journal of Surgical Pathology 18: 992-998.

Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.