In order to address the debatable prognostic role of MYC rearrangements in diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone, we evaluated MYC rearrangements by fluorescence in situ hybridization in 563 cases using break-apart probes and IGH/MYC dual-fusion probes. Concurrent BCL2 and BCL6 aberrations were also assessed. Data were correlated with clinicopathological variables and prognostic parameters. MYC rearrangements were observed in 39/432 evaluable cases (9%), including 4 rearrangements detectable only with the dual-fusion probes, 15 detectable only with the break-apart probes and 20 detectable with both dual-fusion probes and break-apart probes. MYC rearrangements correlated with germinal center B-cell origin (P=0.02), MYC protein expression (P=0.032), and larger tumor mass size (P=0.0003). Patients with MYC rearrangements were more likely to be treatment resistant (P<0.0001). All types of MYC rearrangements were associated with poorer disease-specific survival, that is, 20/39 dead, median disease-specific survival 42 months, compared with 98/393 dead among the non-rearranged cases, median disease-specific survival not reached (P=0.0002). Cases with MYC rearrangements that overexpressed MYC protein were at risk with respect to disease-specific survival independent of the International Prognostic Index (P=0.046 and P<0.001, respectively). Presence of concurrent BCL2 aberrations but not of BCL6 aberrations was prognostically additive. Radiotherapy seemed to diminish the prognostic effects of MYC rearrangements in diffuse large B-cell lymphoma patients since only 2/10 irradiated patients with MYC rearrangements died of/with disease, compared with 16/28 non-irradiated patients with MYC rearrangements. We conclude that MYC rearrangements add prognostic information for individual risk estimation and such cases might represent a distinct, biologically determined disease subgroup.

Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

Visco, Carlo;
2014-01-01

Abstract

In order to address the debatable prognostic role of MYC rearrangements in diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone, we evaluated MYC rearrangements by fluorescence in situ hybridization in 563 cases using break-apart probes and IGH/MYC dual-fusion probes. Concurrent BCL2 and BCL6 aberrations were also assessed. Data were correlated with clinicopathological variables and prognostic parameters. MYC rearrangements were observed in 39/432 evaluable cases (9%), including 4 rearrangements detectable only with the dual-fusion probes, 15 detectable only with the break-apart probes and 20 detectable with both dual-fusion probes and break-apart probes. MYC rearrangements correlated with germinal center B-cell origin (P=0.02), MYC protein expression (P=0.032), and larger tumor mass size (P=0.0003). Patients with MYC rearrangements were more likely to be treatment resistant (P<0.0001). All types of MYC rearrangements were associated with poorer disease-specific survival, that is, 20/39 dead, median disease-specific survival 42 months, compared with 98/393 dead among the non-rearranged cases, median disease-specific survival not reached (P=0.0002). Cases with MYC rearrangements that overexpressed MYC protein were at risk with respect to disease-specific survival independent of the International Prognostic Index (P=0.046 and P<0.001, respectively). Presence of concurrent BCL2 aberrations but not of BCL6 aberrations was prognostically additive. Radiotherapy seemed to diminish the prognostic effects of MYC rearrangements in diffuse large B-cell lymphoma patients since only 2/10 irradiated patients with MYC rearrangements died of/with disease, compared with 16/28 non-irradiated patients with MYC rearrangements. We conclude that MYC rearrangements add prognostic information for individual risk estimation and such cases might represent a distinct, biologically determined disease subgroup.
2014
Adult; Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Female; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Prednisone; Prognosis; Proto-Oncogene Proteins c-myc; Risk Assessment; Rituximab; Treatment Outcome; Vincristine; Gene Rearrangement
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/993295
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