Expression of CREB and VEGF, and microvessel density in plasma cell myeloma by immunohistochemistry: Their correlations with clinical and pathological features

Plasma cell myeloma is a monoclonal plasma cell proliferative disorder and remains an incurable malignant neoplasm. Cyclic AMP regulatory element binding protein (CREB) is a transcription factor. Vascular endothelial growth factor (VEGF) is a glycoprotein that plays an important role in both pathogenesis and progression of plasma cell myeloma.This study included the bone marrow paraffin sections of 76 cases of plasma cell myeloma newly diagnosed between 2001-2010. Bone marrow sections were stained with VEGF, Factor VIII, and p300 antibodies that shows CREB expression by immunohistochemical method. The association of CREB and VEGF expressions with microvessel density (MVD) and clinical/laboratory/histopathological features in plasma cell myeloma were examined.High percentage of plasma cell infiltration showed statistical significance with high MVD and high VEGF expression (p=0.02 and p=0.002, respectively). Similar significant association was present for high grade plasma cell infiltration pattern with high MVD and high VEGF expression (p=0.006 and p=0.01, respectively). High MVD was significantly associated with elevated serum CRP (p=0.03). There was significant association between high CREB expression and high MVD (p=0.01). High MVD and high CREB expression showed stastistical trend for higher clinical stage (p=0.2 and p=0.1, respectively). High MVD was significantly associated with poorer prognosis and shorter overall survival than low MVD (p=0.04). Expression of high VEGF and CREB showed statistical trend for poor survival (p=0.2 and p= 0.1, respectively).In conclusion, high microvessel density, VEGF and CREB expression could be correlated with progression of myeloma. Moreover, targeting therapies for angiogenesis, VEGF and CREB could improve overall survival.