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Background: Multiple myeloma (MM) is a heterogeneous and ultimately fatal disease. Risk stratification using prognostic biomarkers is crucial to individualize treatments. We sought to investigate the role of CD99, a transmembrane protein highly expressed in many hematopoietic cells including subpopulations of normal and neoplastic plasma cells, for MM risk stratification. Methods: CD99 expression was measured in paraffin samples of bone marrow and extramedullary biopsies of 170 patients with MM. Patients were divided into those with high score (moderately andstrongly positive) and low score (negative and weakly positive), with all staining being cytoplasmic and/or membranous. Results: High anti-CD99 immunostaining was observed in 72 of 136 (52.9%) bone marrow biopsies and 24 of 87 (27.6%) extramedullary biopsies in MM. High CD99 expression of extramedullary specimens was associated with significantly longer overall survival (OS; p=.016). High CD99 expression of extramedullary specimens was also associated with better prognosis in the nonautologous stem cell transplantation group of MM patients (p=.044). In multivariate analysis, International Staging System stage was an independent prognostic factor, whereas CD99 expression was no longer statistically significant. Conclusions: Expression of CD99 in extramedullary specimens was correlated with longer OS, suggesting that CD99 may be a helpful immunohistochemical marker for risk stratification.

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