title: MYC expression in concert with BCL2 and BCL6 expression predicts outcome in Chinese patients with diffuse large B-cell lymphoma, not otherwise specified.
abstract: 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.
authors.affiliation: Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, China.
authors.forename: Li-Xu
authors.initials: LX
authors.lastname: Yan
authors.affiliation: Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, China.
authors.forename: Yan-Hui
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, China.
authors.forename: Dong-Lan
authors.initials: DL
authors.lastname: Luo
authors.affiliation: Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, China.
authors.forename: Xin-Lan
authors.initials: XL
authors.lastname: Luo
authors.affiliation: Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, China.
authors.forename: Heng-Guo
authors.initials: HG
authors.lastname: Zhuang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols; D002648:Child; D003520:Cyclophosphamide; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D004317:Doxorubicin; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011241:Prednisone; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics; D000069283:Rituximab; D016896:Treatment Outcome; D014750:Vincristine
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
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