title: Does the proliferation fraction help identify mature B cell lymphomas with double- and triple-hit translocations?
abstract: OBJECTIVE
  The entity 'B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL)' refers to B cell neoplasms that share overlapping characteristics of BL and DLBCL. A subset of these 'grey-zone lymphomas' possesses C-MYC and IGH translocations but, in addition, contains additional rearrangements of BCL2 and/or BCL6 genes. The aim of this study was to investigate if the proliferation fraction by Ki67 immunostaining can be used to identify such double-/triple-hit lymphomas.
  
  
  RESULTS
  We studied 492 cases of mature aggressive B cell neoplasms by histology, immunohistochemistry and interphase fluorescence in-situ hybridization (FISH) using break-apart probes against C-MYC, BCL2, BCL6, IGH, MALT1, PAX5 and CCND1. Forty Burkitt lymphomas and 28 cases of MYC(+) double-/triple-hit lymphomas were identified. Of the latter, 77% and 54% displayed proliferation fractions exceeding 75% and 90%, respectively. With a cut-off of >75% by Ki67 immunostaining, the sensitivity and specificity for detection of MYC(+) double/triple translocations was 0.77 and 0.36. Raising the proliferation fraction criterion to >90% improved the specificity to 0.62 at the expense of a low sensitivity of 0.54.
  
  
  CONCLUSIONS
  Immunostaining for Ki67 is not a useful approach to prescreen B cell lymphomas for MYC(+) double/triple translocations.
authors.affiliation: NCCS-VARI Translational Research Laboratory, Singapore.
authors.forename: Emarene
authors.initials: E
authors.lastname: Mationg-Kalaw
authors.forename: Leonard H C
authors.initials: LH
authors.lastname: Tan
authors.forename: Kevin
authors.initials: K
authors.lastname: Tay
authors.forename: Soon Thye
authors.initials: ST
authors.lastname: Lim
authors.forename: Tiffany
authors.initials: T
authors.lastname: Tang
authors.forename: Yvonne Y L
authors.initials: YY
authors.lastname: Lee
authors.forename: Soo Yong
authors.initials: SY
authors.lastname: Tan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002051:Burkitt Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D049109:Cell Proliferation; D003937:Diagnosis, Differential; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D019394:Ki-67 Antigen / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D007143:Immunoglobulin Heavy Chains; D019394:Ki-67 Antigen; C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc