THE VALUE OF IMMUNOHISTOCHEMISTRY
IN THE ASSESSMENT OF BONE MARROW DISORDERS

Attilio Orazi, M.D., FRCPath. and Dennis P. O'Malley, M.D.

ANGIOGENESIS BY IMMUNOHISTOCHEMISTRY It is now well established that solid tumour growth depends on angiogenesis. By using bone marrow biopsy immunostaining with CD34 or other endothelium reactive markers such as vWF and CD31, microvessel density (MVD) may be assessed in various hematologic disorders. Preliminary results obtained in cases of myelodysplastic syndromes suggest a correlation between increased angiogenesis and progression to acute leukaemia. Correlation with the onset of transformation in cases of chronic myeloid leukemia has also been observed (Orazi et al, 2001). In chronic idiopathic myelofibrosis, microvascular proliferation is thought to be associated with the increased egression of progenitor and precursor cells from the bone marrow, their circulation in high number in the peripheral bood, and subsequent development of splenic and extramedullary myeloid metaplasia. In a recent study, we have found evidence that increased marrow vascularity in CIMF is independent of the degree of marrow fibrosis. In summary, ongoing studies support the hypothesis that angiogenesis may play an important role in the pathogenesis of MDSs, MPDs, and possibly acute leukemias. The findings of significantly increased angiogenesis in subtypes of hematologic diseases raises the possibility of a role for antiangiogenetic treatment. Additional work is now warranted to determine what regulates the generation of new vessels in MDS, MPD, and leukaemia. References Hussong et al: Evidence of increased angiogenesis in patients with acute myeloid leukemia. Blood. 2000 1;95:309-13. Lundberg et al: Bone marrow in polycythemia vera, chronic myelocytic leukemia, and myelofibrosis has an increased vascularity. Am J Pathol. 2000;157:15-9. Orazi, A., Shendrik, I., Mansukhani, M.: Increased angiogenesis is associated with aggressive subtypes of myelodysplastic syndromes and disease progression in chronic myeloid leukemia. United States and Canadian Academy of Pathology, 90th Annual Meeting, Atlanta , GA March 3-9, 2001. Orazi, A., Shendrik, I., Servida, P., Ponzoni, M: Angiogenesis in agnogenic myeloid metaplasia. United States and Canadian Academy of Pathology, 90th Annual Meeting, Atlanta , GA March 3-9, 2001. Padro et al: Increased angiogenesis in the bone marrow of patients with acute myeloid leukemia. Blood. 2000;95:2637-44. Perez-Atayde et al: Spectrum of tumor angiogenesis in the bone marrow of children with acute lymphoblastic leukemia. Am J Pathol. 1997;150:815-21. Pruneri et al: Angiogenesis in myelodysplastic syndromes. Br J Cancer. 1999; 81:1398-401. Antibody Species Clone Treatment Alk-1 p80 mo Alk-1 MWO Amyloid A mo mc1   Amyloid P rb     bcl-2 mo 124 MWO CD1a mo 010 MWO CD3 rb   MWO CD4 mo 1F6 MWO CD5 mo CD5/54/B4 MWO CD8 mo CD8/144B MWO CD10 mo 56C6 MWO CD15 mo MMA MWO CD20 mo L26 MWO CD21 mo 1F8 Protease CD23 mo 1B12 MWO CD30 mo BerH2 MWO CD31 mo JC/70A Protease CD34 mo QBEnd10 MWO CD43 mo Leu 22 MWO CD45 mo 2B11+PD7/26 MWO CD56 mo OB11 MWO CD57 mo Leu7 MWO CD68 mo PGM1 MWO CD79 mo JCB117 MWO CD99 / MIC2 mo 013 MWO pan-cytokeratin mo AE1-AE3 MWO pan-cytokeratin mo KL1 MWO Cytokeratin 20 mo Ks.20.8(1) MWO Cytokeratin 7 mo OVL-TL 12/30 MWO Collagen IV mo CIV22 Protease Cyclin D1 mo P2D11F11 MWO B cells mo DBA.44 MWO EBER ISH probe     EMA mo E29 MWO Factor XIIIa rb   Protease Glycophorin A mo JC159 MWO Hemoglobin rb   MWO IgA rb   MWO IgE rb   MWO kappa rb   Protease kappa ISH probe   MWO Ki-67 mo MIB-1 MWO lambda rb   Protease lambda ISH probe   MWO Lysozyme rb   MWO Myeloperoxidase rb   MWO S-100 rb   MWO TdT rb   MWO TIA-1 mo TIA-1 MWO vFW (FVIIIRag) rb   MWO