Notch signaling is implicated in the pathogenesis of
multiple myeloma expressing high level of active
Notch proteins NOTCH1 and JAGGED1 in
tumor plasma cells. We investigated expression of NOTCH1 and JAGGED1 in bone marrow trephine biopsies of 80 newly diagnosed
multiple myeloma and 20
monoclonal gammopathy of undetermined significance patients using immunohistochemical methods. The number of positive
tumor cells was counted per 1000
tumor cells and the intensity of staining was assessed semi quantitatively.
Multiple myelomas expressed NOTCH1 in 92.31% (72/78) and JAGGED1 in 92.21% (71/77) cases. NOTCH1 staining was strong in the majority of cases (59.7%), whereas JAGGED1 was predominately weak (67.6% of cases). In contrast, both markers were negative in all
monoclonal gammopathy of undetermined significance cases. However, upon progression of disease from
monoclonal gammopathy of undetermined significance to
multiple myeloma (seen in 4 patients), analysis of the subsequent bone marrow biopsy showed weak expression of both markers in tumorous plasma cells. Immunohistochemistry results were compared with the pattern of bone marrow infiltration, plasma cell differentiation, and the presence of t(11;14)(q13,q32), t(14;16)(q32;q23),and t(4;14)(p16.3;q23) and overall survival in
multiple myeloma patients. A significant correlation was found between strong NOTCH1 staining in
multiple myeloma plasma cells and the diffuse type of bone marrow infiltration (P = .002) and an immature morphologic type of plasma cells (P = .043). After a median follow-up of 20.3 months, in
multiple myeloma patients no difference in overall survival between NOTCH1 (P = .484) and JAGGED1 (P = .822) positive and negative cases were found. In conclusion, our results indicate importance of NOTCH1 and JAGGED1 expression in plasma cell
neoplasia and a possible diagnostic value of their immunohistochemical evaluation of bone marrow infiltrates for
multiple myeloma.