High nuclear expression of Twist1 in the skeletal extramedullary disease of myeloma patients predicts inferior survival

The aim of the study was to investigate the expression of epithelial to mesenchymal transition (EMT)-inducing transcription factors, including Twist1 and ZEB1, in skeletal extramedullary disease (EMD) of multiple myeloma (MM) patients and to clarify the effects on clinical outcomes. The expression of Twist1 and ZEB1 in the bone marrow (BM) and the masses of skeletal EMD from 70 MM cases with skeletal EMD and 30 MM patients without skeletal EMD were determined by immunohistochemistry. The results demonstrated that the percentage of high nuclear staining for Twist1 was 24.3% (17/70) in skeletal EMD, which was significantly higher than in the BM of these patients as well as those without skeletal EMD (P = 0.030 and P = 0.011). The microvessel density (MVD, P = 0.004) was significantly higher in patients with high nuclear expression of Twist1 (Twist1-high) than in those with low expression. Patients with Twist1-high experienced a lower rate of progression-free survival (PFS, 11.8% vs. 35.0%, P = 0.000) and overall survival (OS, 52.5% vs. 83.7%, P = 0.001) compared to those with low expression. Multivariate analysis showed that Twist1-high was independently associated with inferior PFS (HR = 2.161; 95%CI: 1.116-4.183; P = 0.022) and OS (HR = 3.111; 95%CI: 1.114-8.685; P = 0.030). We concluded that Twist1-high is associated with a poor prognosis and may be correlated with angiogenesis in the skeletal EMD of MM patients.