期刊
MODERN PATHOLOGY
卷 27, 期 7, 页码 958-971出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/modpathol.2013.214
关键词
diffuse large B-cell lymphoma; FISH; germinal center B-cell; MYC; prognosis; rearrangement; translocation
类别
资金
- Zurich Stiftung zur Krebsbekaempfung [269]
- Krebsliga Beider Basel
- University of Texas MD Anderson Cancer Center Institutional R D Fund
- Institutional Research Grant Award
- MD Anderson Lymphoma SPORE Research Development Program Award
- National Cancer Institute
- MD Anderson Cancer Center Support [CA016672]
- National Institute of Health [R01CA138688, 1RC1CA146299, P50CA136411, P50CA142509]
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.
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