title: The BCL2 E17 and SP66 antibodies discriminate 2 immunophenotypically and genetically distinct subgroups of conventionally BCL2-"negative" grade 1/2 follicular lymphomas.
abstract: Follicular lymphoma (FL) is characterized by the translocation t(14;18)(q32;q21) resulting in constitutive overexpression of BCL2. However, in 10% to 15% of FL grade 1/2, immunohistochemical staining for BCL2 remains negative. To analyze the incidence of BCL2 negativity and the underlying molecular mechanisms in FL grade 1/2, BCL2 expression was investigated with 3 antibodies (clones 100D5, E17, SP66). The presence of a break in the BCL2 locus was determined by fluorescence in situ hybridization. The region of the BCL2 gene where the epitope of the standard BCL2 antibody resides was sequenced. Twenty-two (9.2%) of 240 identified cases of FL grade 1/2 were negative with the standard BCL2 antibody. Of these, 12 cases (55%) carried a break in the BCL2 gene locus, which, in all but one case, correlated with BCL2 expression using the alternative antibodies E17 and SP66 and with missense mutations of BCL2. Ten (45%) of the 22 cases had an intact BCL2 gene locus; 2 cases carried a BCL6/IGH translocation. All 10 cases were negative for the E17/SP66 antibodies and showed a wild-type sequence of BCL2. Six of these showed an aberrant phenotype, with CD10 negativity (30%) or CD23 expression (30%). In summary, the alternative E17/SP66 antibodies identify 2 immunohistochemically and genetically distinct subgroups of BCL2-"negative" FL grade 1/2.
authors: Institute of Pathology, Comprehensive Cancer Center, University of Tübingen, D-72076 Tübingen, Germany.
authors: Patrick
authors: P
authors: Adam
authors: Rosalie
authors: R
authors: Baumann
authors: Janine
authors: J
authors: Schmidt
authors: Sabrina
authors: S
authors: Bettio
authors: Katja
authors: K
authors: Weisel
authors: Irina
authors: I
authors: Bonzheim
authors: Falko
authors: F
authors: Fend
authors: Leticia
authors: L
authors: Quintanilla-Martínez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D002999:Clone Cells; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008224:Lymphoma, Follicular / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D017354:Point Mutation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D014178:Translocation, Genetic
chemical_list: D004273:DNA, Neoplasm; D019253:Proto-Oncogene Proteins c-bcl-2
keywords: BCL2 E17 and SP66 antibodies; BCL2 mutations; BCL2-negative follicular lymphoma; t(14;18) translocation