MYC translocation and/or BCL 2 protein expression are associated with poor prognosis in diffuse large B‐cell lymphoma

• Published in: Cancer science Vol. 107; no. 6; pp. 853 - 861
• Main Authors: Kawamoto, Keisuke, Miyoshi, Hiroaki, Yoshida, Noriaki, Nakamura, Naoya, Ohshima, Koichi, Sone, Hirohito, Takizawa, Jun
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.06.2016; John Wiley and Sons Inc
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; B-cell lymphoma; Bcl-6 protein; BCL2; BCL6; Chemotherapy; Copy number; Cyclophosphamide; Cyclophosphamide - therapeutic use; diffuse large B‐cell lymphoma; Doxorubicin; Doxorubicin - therapeutic use; Female; Gene expression; Genes, myc; Humans; Immunoglobulins; Lymphocytes B; Lymphoma; Lymphoma, Large B-Cell, Diffuse - diagnosis; Lymphoma, Large B-Cell, Diffuse - genetics; Male; Medical prognosis; Medical research; Middle Aged; Monoclonal antibodies; MYC; Myc protein; Original; Prednisolone; Prednisolone - therapeutic use; Prognosis; prognostic factor; Protein expression; Proteins; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-6 - genetics; Rituximab; Rituximab - therapeutic use; Studies; Targeted cancer therapy; Translocation; Translocation, Genetic - genetics; Vincristine; Vincristine - therapeutic use; Young Adult; Japan; Germany; BCL2; diffuse large B-cell lymphoma; BCL6; prognostic factor; MYC
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.12942

Genomic alterations and protein expression levels have been established as prognostic factors for survival in patients with diffuse large B‐cell lymphoma (DLBCL). In particular, double‐hit DLBCL (DHL), which exhibits translocations in MYC and BCL2 and/or BCL6, is known to be associated with a poor prognosis. However, the clinical significance of gene alterations and protein expression levels for MYC, B‐cell lymphoma (BCL)2, and BCL6 are unclear. In this study, we analyzed 61 adult patients diagnosed with DLBCL without DHL, who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone, or similar regimens. There were no differences in the distribution of MYC expression rates among the different MYC gene statuses. In log–rank tests, MYC translocation was a prognostic factor for overall survival (OS; P = 0.011), whereas BCL2 and BCL6 translocation were not prognostic indicators (P = 0.999 and P = 0.925, respectively). Although the expression levels of MYC and BCL6 were not significantly associated with OS, the expression of BCL2 was a prognostic factor for OS (P = 0.027). Furthermore, copy number gains in the MYC, BCL2, and BCL6 genes did not affect OS. MYC translocation (hazard ratio, 4.769; range, 1.518–14.98; P = 0.007) and BCL2 protein expression (hazard ratio, 3.072; range, 1.002–9.413; P = 0.049) were independent prognostic factors for survival in multivariate analyses. In conclusion, MYC translocation and BCL2 expression may need to be investigated at the initial diagnosis to predict prognosis in patients with DLBCL. In this study, we examined the relationships between genomic alterations and protein expression of MYC, BCL2, and BCL6 in diffuse large B‐cell lymphoma. Although the clinical utility of protein expression and translocation of MYC and BCL2 is controversial in diffuse large B‐cell lymphoma, we confirmed that MYC translocation, as detected by fluorescence in situ hybridization, and BCL2 expression, as analyzed by immunohistochemistry, were important for predicting survival.