PMID- 25090026 OWN - NLM STAT- MEDLINE DCOM- 20151116 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 8 DP - 2014 TI - MYC expression in concert with BCL2 and BCL6 expression predicts outcome in Chinese patients with diffuse large B-cell lymphoma, not otherwise specified. PG - e104068 LID - 10.1371/journal.pone.0104068 [doi] LID - e104068 AB - Recent studies provide convincing evidence that a combined immunohistochemical or fluorescence in situ hybridization (FISH) score of MYC, BCL2, BCL6 proteins and MYC translocations predicted outcome in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, by far, all these researches are based on Western populations. Therefore, we investigate the prognostic relevance of MYC-, BCL2- and BCL6-rearrangements and protein expression by immunohistochemistry and FISH from 336 de novo DLBCL, NOS treated with CHOP or R-CHOP. Breaks in MYC and BCL6, and fusion in IGH/BCL2 were detected in 9.7%, 20.0%, and 11.1% of the cases, respectively, and were not significantly associated with clinical outcomes. Protein overexpression of MYC (>/=40%), BCL2 (>/=70%) and BCL6 (>/=50%) was encountered in 51%, 51% and 36% of the tumors, respectively. On the basis of MYC, BCL2 and BCL6 expression, double-hit scores (DHSs) and triple-hit score (THS) were assigned to all patients with DLBCL. Patients with high MYC/BCL2 DHS, high MYC/BCL6 DHS and high THS had multiple adverse prognostic factors including high LDH level, poor performance status, advanced clinical stage, high International Prognostic Index (IPI) score, and non-germinal center B-cell. In univariate analysis, high MYC/BCL2 DHS, high MYC/BCL6 DHS and high THS were associated with inferior OS and PFS in both CHOP and R-CHOP cohorts (P<0.05). The highly significant correlations with OS and PFS were maintained in multivariate models that controlled for IPI (P<0.05). DLBCLs with high DHSs and high THS share the clinical features and poor prognosis of double-hit lymphoma (P>0.05). These data together suggest that the immunohistochemical DHSs and THS defined a large subset of DLBCLs with double-hit biology and was strongly associated with poor outcome in patients treated with R-CHOP or CHOP. FAU - Yan, Li-Xu AU - Yan LX AD - Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, China. FAU - Liu, Yan-Hui AU - Liu YH AD - Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, China. FAU - Luo, Dong-Lan AU - Luo DL AD - Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, China. FAU - Zhang, Fen AU - Zhang F AD - Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, China. FAU - Cheng, Yu AU - Cheng Y AD - Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, China. FAU - Luo, Xin-Lan AU - Luo XL AD - Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, China. FAU - Xu, Jie AU - Xu J AD - Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, China. FAU - Cheng, Jie AU - Cheng J AD - Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, China. FAU - Zhuang, Heng-Guo AU - Zhuang HG AD - Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140804 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antibodies, Monoclonal, Murine-Derived) RN - 0 (BCL6 protein, human) RN - 0 (DNA-Binding Proteins) RN - 0 (MYC protein, human) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Proto-Oncogene Proteins c-bcl-6) RN - 0 (Proto-Oncogene Proteins c-myc) RN - 0 (R-CHOP protocol) RN - 4F4X42SYQ6 (Rituximab) RN - 5J49Q6B70F (Vincristine) RN - 80168379AG (Doxorubicin) RN - 8N3DW7272P (Cyclophosphamide) RN - VB0R961HZT (Prednisone) SB - IM EIN - PLoS One. 2014;9(10):e110724 EIN - PLoS One. 2018 Dec 26;13(12):e0210027. PMID: 30586419 MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal, Murine-Derived MH - Antineoplastic Combined Chemotherapy Protocols MH - Child MH - Cyclophosphamide MH - DNA-Binding Proteins/*biosynthesis/genetics MH - Disease-Free Survival MH - Doxorubicin MH - Female MH - Gene Expression Regulation, Neoplastic MH - Humans MH - In Situ Hybridization, Fluorescence MH - Lymphoma, Large B-Cell, Diffuse/drug therapy/*genetics/pathology MH - Male MH - Middle Aged MH - Prednisone MH - Prognosis MH - Proto-Oncogene Proteins c-bcl-2/*biosynthesis/genetics MH - Proto-Oncogene Proteins c-bcl-6 MH - Proto-Oncogene Proteins c-myc/*biosynthesis/genetics MH - Rituximab MH - Treatment Outcome MH - Vincristine PMC - PMC4121314 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/08/05 06:00 MHDA- 2015/11/17 06:00 PMCR- 2014/08/04 CRDT- 2014/08/05 06:00 PHST- 2014/03/25 00:00 [received] PHST- 2014/07/05 00:00 [accepted] PHST- 2014/08/05 06:00 [entrez] PHST- 2014/08/05 06:00 [pubmed] PHST- 2015/11/17 06:00 [medline] PHST- 2014/08/04 00:00 [pmc-release] AID - PONE-D-14-13280 [pii] AID - 10.1371/journal.pone.0104068 [doi] PST - epublish SO - PLoS One. 2014 Aug 4;9(8):e104068. doi: 10.1371/journal.pone.0104068. eCollection 2014.