MYD88 expression and L265P mutation in diffuse large B-cell lymphoma

• Published in: Human pathology Vol. 44; no. 7; pp. 1375 - 1381
• Main Authors: Choi, Jung-Woo, MD, PhD, Kim, Younghye, MD, Lee, Ju-Han, MD, PhD, Kim, Young-Sik, MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2013; Elsevier Limited
• Subjects: Age; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cloning; Confidence intervals; Disease Progression; DNA Mutational Analysis; DNA, Neoplasm - genetics; Female; Gene Expression Regulation, Neoplastic; Humans; Lymphoma; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - metabolism; Lymphoma, Large B-Cell, Diffuse - mortality; Lymphoma, Large B-Cell, Diffuse - pathology; Male; Middle Aged; Multivariate analysis; Mutation; MYD88; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - metabolism; Neoplasm Recurrence, Local; Non–Hodgkin lymphoma; Pathology; Point Mutation; Polymerase Chain Reaction; Proteins; Republic of Korea - epidemiology; Survival Rate; Tissue Array Analysis; Republic of Korea; MYD88; Mutation; Non–Hodgkin lymphoma
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2012.10.026

Summary Activated B-cell–like subtype of diffuse large B-cell lymphoma (DLBCL) is characterized by chronic active B-cell receptor signaling and a constitutive activation of the nuclear factor κ B pathway. As a driving force of nuclear factor κ B overactivity, myeloid differentiation primary response gene 88 ( MYD88 ) L265P mutation occurs in activated B-cell–like DLBCL. However, the MYD88 L265P mutation has not yet been studied in conjunction with MYD88 protein expression in DLBCL cases. Thus, we investigated MYD88 expression in 124 DLBCL specimens by immunohistochemistry. In addition, the MYD88 L265P mutation was examined by polymerase chain reaction and direct DNA sequencing. MYD88 was overexpressed in 38.7% (48/124) of DLBCL cases. MYD88 was expressed in the cytoplasm of lymphoma cells. MYD88 overexpression was associated with older age ( P = .016) and tumor recurrence ( P = .007). In univariate analysis, MYD88 overexpression was correlated with shortened disease-free survival (DFS) of DLBCL ( P = .013) and non–germinal center B-cell–like DLBCL ( P = .034). In multivariate analysis, MYD88 overexpression was an independent factor for reduced DFS ( P = .025). MYD88 L265P mutation was found in 6.5% (8/124) of DLBCL cases. All but 1 case were of non–germinal center B-cell–like subtype. The MYD88 L265P mutation was not associated with MYD88 expression (Spearman ρ = −0.074) and clinicopathologic parameters of DLBCL. The data indicate that high MYD88 expression is significantly associated with tumor recurrence and shortened DFS in patients with DLBCL. In addition, the incidence of MYD88 L265P mutation in Korea is much lower than previously reported. Thus, MYD88 may be crucial for lymphoma progression, independent of MYD88 L265P mutation.