Predictive Immune Markers for Disease Progression in Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance

Abstract

Multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM, are plasma cell neoplasms. The evolution of the treatment of MM in recent years has dramatically improved the outcome for these patients. Currently, multidisciplinary studies are being conducted to elucidate the etiopathogenesis of the disease and develop specific treatment agents and prognostic markers. The present study investigates the relationships between immunoexpression of CD138, Pan-Ras, CCL-3, DKK-1, and MUM-1 and disease progression in cases of MM and MGUS. Immunohistochemical staining for CD138, Pan-Ras, CCL-3, DKK-1, and MUM-1 were performed on bone marrow biopsy samples from 94 MM and 20 MGUS patients diagnosed between 2011 and 2018. Immunohistochemical results were examined semiquantitatively, and the associations between the immunohistochemical, clinical, and biochemical markers utilized for MM and MGUS patient staging were analyzed. Pan-Ras, DKK-1, and MUM-1 staining results were significantly higher in MM compared to MGUS (p=0.005, 0.001, and 0.001, respectively). The mean CCL-3 expression in patients with MGUS was 23.15%, while it was 18.68% in cases of MM (p=0.413). CCL-3 expression was significantly higher in high-risk MGUS cases compared to other risk groups according to the Mayo Clinic Risk Stratification for MGUS. According to the International Staging System and the Revised International Staging System, CD138 expression was higher among stage II and stage III patients than stage I patients. Differences in Pan-Ras, MUM-1, DKK-1, and CCL-3 expressions between MM and MGUS suggest that these molecules may play a role in the progression of MGUS to MM. CCL-3, an immunohistochemical marker, may be predictive of MGUS progression, while CD138 is associated with more advanced stages of MM.