MYC Protein Expression Is Detected in Majority of Multiple Myeloma but Not in Monoclonal Gammopathy of Undetermined Significance (MGUS)
Ruobing Xiao, Karen Dresser, Bruce Woda, Hongbo Yu. University of Massachusetts Medical School, Worcester, MA
Background: Multiple myeloma is a bone marrow-based plasma cell neoplasm associated with an M protein in serum or urine. Recent studies have shown that most patients with multiple myeloma have a preceding monoclonal gammopathy of undetermined significance (MGUS). A number of genetic events in multiple myeloma have been described. However, these abnormalities are already present in MGUS. These findings suggest that there are secondary events which contribute to the progression from MGUS to myeloma. Recently gene expression array analysis has revealed that MYC activation signature is detected in myeloma, but not in MGUS.
Design: Our study includes bone marrow core biopsies from 27 patients with newly diagnosed multiple myeloma, and from 30 patients with clinical diagnosis of MGUS. We performed immunohistochemical studies using membrane CD138 and nuclear MYC double staining. Student's t-test was performed for analyzing MYC expression in plasma cells in the myeloma group in comparison with MGUS group. P<0.05 was considered as significant.
Results: Our study demonstrated nuclear MYC expression was detected in CD138-positive plasma cells in 23 out of 27 (85%) patients in the myeloma group. However, among all 30 patients with MGUS, none of the bone marrow samples exhibited MYC expression in plasma cells. Student's t-test was performed to compare the percentages of MYC-positive plasma cells in both groups, and P value was less than 0.0001. Control samples with polytypic plasmacytosis showed no MYC expression. The total plasma cells in the bone marrow core biopsies range from 10% to 90% in the myeloma group, and from 5% to 15% in the MGUS group. Among the bone marrow samples from patients with multiple myeloma, the percentages of MYC-positive plasma cells vary from case to case, ranging from 0 to 90% with a mean of 42.9%. Among 27 myeloma samples, there were 8 with >70% of MYC-positive plasma cells, 9 with 30-70% of MYC-positive plasma cells, and 10 with <30% of MYC-positive plasma cells.
Conclusions: Our study has demonstrated that MYC protein expression is detected in majority of bone marrow biopsies from patients with multiple myeloma, not in MGUS (P value < 0.0001). Our findings suggest that MYC activation may be involved in secondary genetic events, which are associated with the progression from MGUS to multiple myeloma. In addition, evaluation of MYC expression in plasma cells can be useful in detecting residual diseases in patients with MYC-positive myeloma.
Monday, March 4, 2013 11:30 AM
Proffered Papers: Section C, Monday Morning