The BCL2 E17 and SP66 antibodies discriminate 2 immunophenotypically and genetically distinct subgroups of conventionally BCL2-"negative" grade 1/2 follicular lymphomas

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The BCL2 E17 and SP66 antibodies discriminate 2 immunophenotypically and genetically distinct subgroups of conventionally BCL2-"negative" grade 1/2 follicular lymphomas. / Adam, Patrick; Baumann, Rosalie; Schmidt, Janine; Bettio, Sabrina; Weisel, Katja; Bonzheim, Irina; Fend, Falko; Quintanilla-Martínez, Leticia.

in: HUM PATHOL, Jahrgang 44, Nr. 9, 09.2013, S. 1817-26.

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@article{fd307eb5cb934982834395c96ed4bb68,
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. ",
keywords = "Adult, Aged, Aged, 80 and over, Chromosomes, Human, Pair 14, Chromosomes, Human, Pair 18, Clone Cells, DNA Mutational Analysis, DNA, Neoplasm, Female, Gene Expression Regulation, Neoplastic, Humans, In Situ Hybridization, Fluorescence, Lymph Nodes, Lymphoma, Follicular, Male, Middle Aged, Neoplasm Grading, Point Mutation, Proto-Oncogene Proteins c-bcl-2, Translocation, Genetic, Journal Article, Research Support, Non-U.S. Gov't",
author = "Patrick Adam and Rosalie Baumann and Janine Schmidt and Sabrina Bettio and Katja Weisel and Irina Bonzheim and Falko Fend and Leticia Quintanilla-Mart{\'i}nez",
note = "Copyright {\textcopyright} 2013 Elsevier Inc. All rights reserved.",
year = "2013",
month = sep,
doi = "10.1016/j.humpath.2013.02.004",
language = "English",
volume = "44",
pages = "1817--26",
journal = "HUM PATHOL",
issn = "0046-8177",
publisher = "W.B. Saunders Ltd",
number = "9",

}

RIS

TY - JOUR

T1 - The BCL2 E17 and SP66 antibodies discriminate 2 immunophenotypically and genetically distinct subgroups of conventionally BCL2-"negative" grade 1/2 follicular lymphomas

AU - Adam, Patrick

AU - Baumann, Rosalie

AU - Schmidt, Janine

AU - Bettio, Sabrina

AU - Weisel, Katja

AU - Bonzheim, Irina

AU - Fend, Falko

AU - Quintanilla-Martínez, Leticia

N1 - Copyright © 2013 Elsevier Inc. All rights reserved.

PY - 2013/9

Y1 - 2013/9

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Chromosomes, Human, Pair 14

KW - Chromosomes, Human, Pair 18

KW - Clone Cells

KW - DNA Mutational Analysis

KW - DNA, Neoplasm

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - In Situ Hybridization, Fluorescence

KW - Lymph Nodes

KW - Lymphoma, Follicular

KW - Male

KW - Middle Aged

KW - Neoplasm Grading

KW - Point Mutation

KW - Proto-Oncogene Proteins c-bcl-2

KW - Translocation, Genetic

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.humpath.2013.02.004

DO - 10.1016/j.humpath.2013.02.004

M3 - SCORING: Journal article

C2 - 23642737

VL - 44

SP - 1817

EP - 1826

JO - HUM PATHOL

JF - HUM PATHOL

SN - 0046-8177

IS - 9

ER -