STAT3 expression is associated with poor survival in non-elderly adult patients with newly diagnosed multiple myeloma

Signal transducer and activator of transcription 3 (STAT3) is not only a key signaling molecule in the regulation of growth but is also involved in malignant transformation. We investigated the prognostic significance of STAT3 expression in 94 non-elderly adult patients (aged 38 to 65 yr) with newly diagnosed multiple myeloma (MM). Tumor cell-specific phosphotyrosine-STAT3 (PY-STAT3) expression at the time of diagnosis was evaluated with dual immunohistochemical (IHC) staining for PY-STAT3 and CD138. PY-STAT3 positivity was detected in 10 patients (10.6%), including three who showed strong expression. PY-STAT3-positive patients had higher serum C-reactive protein and calcium levels at diagnosis than did PY-STAT3-negative patients. PY-STAT3 positivity had predictive value for poor progression-free survival (PFS; =0.001) and overall survival (OS; =0.003). Among the 60 patients who received frontline autologous stem cell transplantation, PY-STAT3-positive patients had poorer PFS than did PY-STAT3-negative patients (4.2 vs. 19.2 mo, respectively; =0.013). Multivariate analysis identified PY-STAT3 expression as an independent prognostic factor for PFS (relative risk [RR]=2.706, =0.014) and OS (RR=3.091, =0.044). These data show that PY-STAT3 positivity, as determined using dual IHC, is a marker of poor prognosis in non-elderly adult patients with MM.