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

Research output: Contribution to journalArticle

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Abstract

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 κB pathway. As a driving force of nuclear factor κB 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.

Original languageEnglish
Pages (from-to)1375-1381
Number of pages7
JournalHuman Pathology
Volume44
Issue number7
DOIs
Publication statusPublished - 2013 Jul 1

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Lymphoma, Large B-Cell, Diffuse
Mutation
B-Lymphocytes
Disease-Free Survival
Lymphoma
Recurrence
Korea
DNA Sequence Analysis
Neoplasms
Cytoplasm
Multivariate Analysis
Immunohistochemistry
Polymerase Chain Reaction

Keywords

  • Mutation
  • MYD88
  • Non-Hodgkin lymphoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

MYD88 expression and L265P mutation in diffuse large B-cell lymphoma. / Choi, Jung-Woo; Kim, Younghye; Lee, Ju-Han; Kim, Young Sik.

In: Human Pathology, Vol. 44, No. 7, 01.07.2013, p. 1375-1381.

Research output: Contribution to journalArticle

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abstract = "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 κB pathway. As a driving force of nuclear factor κB 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.",
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