title: Follicular lymphoma lacking the t(14;18)(q32;q21): identification of two disease subtypes.
abstract: The clinical and pathological features, including karyotype data and BCL2 protein expression pattern, of follicular lymphoma without a t(14;18)(q32;q21) have not been well defined. We have identified and conducted a detailed analysis of 50 cases with follicular lymphoma who lack the t(14;18). Fluorescent in situ hybridization (FISH) analysis was used to exclude cases with a cryptic IGH/BCL2 rearrangement. BCL2 protein expression level was assessed by immunohistochemistry. The karyotypes were assessed for recurrent sites of structural rearrangement, duplications and deletions on a band-by-band basis, and compared with a large cohort of cases with t(14;18). A distinct pattern of chromosomal alterations was identified in the cases without t(14;18). BCL2 protein overexpression was detected in 33% of 49 tested cases. In this minority, the karyotypes frequently showed increased copies of chromosome 18. The majority of cases (67%) did not show BCL2 overexpression and were characterized prominently by the presence of t(3;14)(q27;q32), implying a role for BCL6. Follicular lymphomas that lack a t(14;18) were segregated into two subgroups with distinct cytogenetic, phenotypic and possibly clinical features: one with BCL2 protein overexpression not related to an IGH/BCL2 rearrangement and a second without BCL2 overexpression. Objective identification of BCL2 expression level as well as BCL2 and BCL6 status by cytogenetic or FISH analysis has potential clinical utility and may yield insights into alternative genetic mechanisms associated with B-cell lymphomas with a follicular growth pattern.
authors.affiliation: Pathology and Laboratory Medicine Division, British Columbia Cancer Agency, Canada. dhorsman@bccancer.bc.ca
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Horsman
authors.forename: Ichiro
authors.initials: I
authors.lastname: Okamoto
authors.forename: Olga
authors.initials: O
authors.lastname: Ludkovski
authors.forename: Nhu
authors.initials: N
authors.lastname: Le
authors.forename: Lana
authors.initials: L
authors.lastname: Harder
authors.forename: Stefan
authors.initials: S
authors.lastname: Gesk
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Mukesh
authors.initials: M
authors.lastname: Chhanabhai
authors.forename: Laurie
authors.initials: L
authors.lastname: Sehn
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014178:Translocation, Genetic
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2