Evidence map›Paper›PMID 25090918›Full record

ArticleHuman pathology2014

BCL2 antibodies targeted at different epitopes detect varying levels of protein expression and correlate with frequent gene amplification in diffuse large B-cell lymphoma.

Samantha L Kendrick, Lucas Redd, Andrea Muranyi, Leigh A Henricksen, Stacey Stanislaw, Lynette M Smith, Anamarija M Perry, Kai Fu, Dennis D Weisenburger, Andreas Rosenwald and 13 more

Open access · greenAbstract read
In one paragraph

Article in Human pathology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. HighCells · 2023
    Article
  6. Follicular lymphoma: updates for pathologists.Journal of pathology and translational medicine · 2022
    Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Diagnostic and predictive biomarkers for lymphoma diagnosis and treatment in the era of precision medicine.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2016
    Review
  17. Article
  18. Article
  19. Genetic lesions in diffuse large B-cell lymphomas.Annals of oncology : official journal of the European Society for Medical Oncology · 2015
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors at 15 institutions in 5 countries.

Samantha L KendrickDepartment of Pathology, University of Arizona, Tucson, AZ 85724.
Lucas ReddDepartment of Pathology, University of Arizona, Tucson, AZ 85724.
Andrea MuranyiVentana Medical Systems, Inc., Tucson, AZ 85755.
Leigh A HenricksenVentana Medical Systems, Inc., Tucson, AZ 85755.
Stacey StanislawVentana Medical Systems, Inc., Tucson, AZ 85755.
Lynette M SmithDepartment of Biostatistics, University of Nebraska Medical Center, Omaha, NE 68198.
Anamarija M PerryDepartment of Pathology, University of Manitoba, Winnipeg, MB, Canada R3A 1R9.
Kai FuDepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198.
Dennis D WeisenburgerDepartment of Pathology, City of Hope Medical Center, Duarte, CA 91010.
Andreas RosenwaldDepartment of Pathology, University of Wuerzburg, Wuerzburg, Germany 97070.
German OttDepartment of Clinical Pathology, Robert-Bosch-Krankenhaus, and Dr. Margarete Fischer-Bosch-Institu fur Klinische Pharmakologie (IKP), 70376 Stuttgart, Germany.
Randy D GascoyneDepartment of Pathology and Laboratory Medicine, British Columbia Cancer Agency, Vancouver, BC, Canada V5Z 4E6.
Elaine S JaffeLaboratory of Pathology, National Cancer Institute, Bethesda, MD 20892.
Elías CampoDepartment of Pathology, Hospital Clínic, Barcelona, Spain 08028.
Jan DelabieDepartment of Pathology, The Norwegian Radium Hospital, University of Oslo, Oslo, Norway 0310.
Rita M BrazielDepartment of Clinical Pathology, Oregon Health & Science University, Portland, OR 97239.
James R CookDepartment of Molecular Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, OH 44195.
Raymond R TubbsDepartment of Molecular Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, OH 44195.
Louis M StaudtMetabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892.
Wing Chung ChanDepartment of Pathology and Laboratory Medicine, British Columbia Cancer Agency, Vancouver, BC, Canada V5Z 4E6.
Christian SteidlDepartment of Pathology and Laboratory Medicine, British Columbia Cancer Agency, Vancouver, BC, Canada V5Z 4E6.
Thomas M GroganDepartment of Pathology, University of Arizona, Tucson, AZ 85724; Ventana Medical Systems, Inc., Tucson, AZ 85755.
Lisa M RimszaDepartment of Pathology, University of Arizona, Tucson, AZ 85724. Electronic address: lrimsza@pathology.arizona.edu.
Ventana Research Corporation (United States) · USUniversity of Arizona · USBC Cancer Agency · CACleveland Clinic · USUniversity of Nebraska Medical Center · USCenter for Cancer Research · USCity Of Hope National Medical Center · USDr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology · DENational Cancer Institute · USOregon Health & Science University · USUniversitat de Barcelona · ESUniversity of British Columbia · CAUniversity of Manitoba · CAUniversity of Oslo · NOUniversity of Würzburg · DE

Funding

Molecular diagnosis and outcome prediction in lymphomaZIABC011006 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI STAUDT, LOUIS · 2009 to 2025
$21.0M
Integrative Cancer Scholars Training GrantT32CA009213 · NCI · UNIVERSITY OF ARIZONA · PI CAREW, JENNIFER S, CURIEL-LEWANDROWSKI, CLARA · 1985 to 2024
$8.6M
Molecular Diagnosis and Prognosis in Aggressive LymphomaU01CA157581 · NCI · UNIVERSITY OF ARIZONA · PI RIMSZA, LISA · 2011 to 2015
$3.1M
NCI NIH HHS CA009213NCI NIH HHS CA157581NCI NIH HHS T32 CA009213NCI NIH HHS U01 CA157581
6 · The paper itself

Abstract

Patients with aggressive, BCL2 protein-positive (+) diffuse large B-cell lymphoma (DLBCL) often experience rapid disease progression that is refractory to standard therapy. However, there is potential for false-negative staining of BCL2 using the standard monoclonal mouse 124 antibody that hinders the identification of these high-risk DLBCL patients. Herein, we compare 2 alternative rabbit monoclonal antibodies (E17 and SP66) to the 124 clone in staining for BCL2 in formalin-fixed, paraffin-embedded DLBCL tissues. Overall, in 2 independent DLBCL cohorts, E17 and SP66 detected BCL2 expression more frequently than 124. In the context of MYC expression, cases identified as BCL2 (+) with SP66 demonstrated the strongest correlation with worse overall survival. The 124 clone failed to detect BCL2 expression in the majority of translocation (+), amplification (+), and activated B-cell DLBCL cases in which high levels of BCL2 protein are expected. Using dual in situ hybridization as a new tool to detect BCL2 translocation and amplification, we observed similar results as previously reported for fluorescence in situ hybridization for translocation but a higher amplification frequency, indicating that BCL2 amplification may be underreported in DLBCL. Among the discrepant cases, phosphorylation of BCL2 at T69 and/or S70 was more common than in the concordant cases and may contribute to the 124 false negatives, in addition to previously associated mutations within the epitope region. The accurate detection of BCL2 expression is important in the prognosis and treatment of DLBCL particularly with new anti-BCL2 therapies.

Indexed as

Antibodies, MonoclonalGene AmplificationAnimalsBiomarkers, TumorEpitopes, B-LymphocyteHumansImmunohistochemistryIn Situ HybridizationLymphoma, Large B-Cell, DiffuseProto-Oncogene Proteins c-bcl-2RabbitsTissue Array AnalysisAntibodies, MonoclonalBiomarkers, TumorEpitopes, B-LymphocyteProto-Oncogene Proteins c-bcl-2BCL2 amplification and translocationBCL2 phosphorylationDiffuse large B-cell lymphomaDual in situ hybridization (dual ISH)E17 and SP66 BCL2 antibodies

Identifiers

PMID25090918
PMCPMC4197184
OpenAlexW2009962689

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.