High interobserver variability of PTEN immunohistochemistry defining PTEN status in low- to intermediate-risk prostate cancer: results of the first German ring trial.

Autor: Hommerding O; Institute of Pathology, University Hospital Bonn, Bonn, Germany., Bernhardt M; Institute of Pathology, University Hospital Bonn, Bonn, Germany., Kreft T; Institute of Pathology, University Hospital Bonn, Bonn, Germany., Scherping A; Institute of Pathology, University Hospital Bonn, Bonn, Germany., Abbas M; Institute of Pathology, University Hospital Muenster, Muenster, Germany., Baretton G; Institute of Pathology, University of Technology Dresden, Dresden, Germany., Bräsen JH; Institute of Pathology, Hannover Medical School, Hannover, Germany., Breyer J; Department of Urology, Caritas Hospital St. Josef, University of Regensburg, Regensburg, Germany., Darr C; Department of Urology, University Medicine Essen, University of Duisburg Essen, Essen, Germany., Dressler FF; Institute of Pathology, University Medical Center Schleswig-Holstein, Lübeck Site, Lübeck, Germany.; Institute of Pathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany., Ellinger J; Department of Urology, University Hospital Bonn, Bonn, Germany., Erber R; Institute of Pathology, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany., Esposito I; Institute of Pathology, Heinrich Heine University and University Hospital of Duesseldorf, Dusseldorf, Germany., Hartmann A; Institute of Pathology, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany., Hartmann W; Institute of Pathology, University Hospital Muenster, Muenster, Germany., Heitplatz B; Institute of Pathology, University Hospital Muenster, Muenster, Germany., Kreipe H; Institute of Pathology, Hannover Medical School, Hannover, Germany., Lafos M; Institute of Pathology, Hannover Medical School, Hannover, Germany., Linxweiler J; Department of Urology, Saarland University, Saarbrücken, Homburg/Saar, Germany., Lopez-Cotarelo C; Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany., Sailer V; Institute of Pathology, University Medical Center Schleswig-Holstein, Lübeck Site, Lübeck, Germany., Reis H; Institute of Pathology, University Medicine Essen, University of Duisburg Essen, Essen, Germany.; Dr. Senckenberg Institute of Pathology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany., Saar M; Current Affiliation: Department of Urology, Aachen University (RWTH), Aachen, Germany.; Department of Urology, Saarland University, Saarbrücken, Homburg/Saar, Germany., Schildhaus HU; Institute of Pathology, University Medicine Essen, University of Duisburg Essen, Essen, Germany.; Discovery Life Sciences, Kassel, Germany., Schlack K; Prostate Center, University Hospital Muenster, Muenster, Germany., Schmid M; Institute for Medical Biometry, Informatics and Epidemiology, University Hospital Bonn, Bonn, Germany., Seidl M; Institute of Pathology, Heinrich Heine University and University Hospital of Duesseldorf, Dusseldorf, Germany., Semjonow A; Prostate Center, University Hospital Muenster, Muenster, Germany., Sommer U; Institute of Pathology, University of Technology Dresden, Dresden, Germany., Stahl PR; Department of Pathology, MSB Medical School Berlin, 14197, Berlin, Germany., Tischler V; Institute of Pathology, University Hospital Bonn, Bonn, Germany., Weber F; Institute of Pathology, University of Regensburg, Regensburg, Germany., Wulf AL; Institute of Pathology, University Hospital Bonn, Bonn, Germany., Wullich B; Department of Urology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany., Kristiansen G; Institute of Pathology, University Hospital Bonn, Bonn, Germany. glen.kristiansen@ukbonn.de.
Jazyk: angličtina
Zdroj: Virchows Archiv : an international journal of pathology [Virchows Arch] 2024 Dec 09. Date of Electronic Publication: 2024 Dec 09.
DOI: 10.1007/s00428-024-03999-y
Abstrakt: The prognostication of individual disease trajectory and selection of optimal therapy in patients with localized, low-grade prostate cancer often presents significant difficulty. The phosphatase and tensin homolog on chromosome 10 (PTEN) has emerged as a potential novel biomarker in this clinical context, based on its demonstrated prognostic significance in multiple retrospective studies. Incorporation into standard clinical practice necessitates exceptional diagnostic accuracy, and PTEN's binary readout-retention or loss-suggests its suitability as a biomarker. This multi-institutional ring trial aimed to validate the diagnostic precision of PTEN immunohistochemistry in localized, low- to intermediate-risk prostate cancer, across ten university pathology institutes in Germany. The trial incorporated 90 cases of patients diagnosed with acinar adenocarcinoma of the prostate of grade groups 1 (n = 8, 8.9%) and 2 (n = 82, 91.1%) post-radical prostatectomy. Remarkably, the interpretation of PTEN immunohistochemistry displayed substantial variation (12.5-51.2% PTEN loss rates) within an identical cohort of prostate cancer. Fluorescence in situ hybridization analysis demonstrated PTEN hemizygous deletions in 5.5% (5/90) of cases. All cases with hemizygous deletions presented a distinct loss of PTEN expression by immunohistochemistry and were unanimously identified as PTEN loss by all participants (sensitivity 100%). However, negative (loss) immunohistochemistry was relatively non-specific for an underlying genomic deletion. Improved inter-observer agreement was observed in a subsequent ring trial. Finally, we identify S473-pAKT immunohistochemistry as a useful marker in equivocal cases. In summary, this multi-institutional ring trial illustrates surprisingly heterogeneous outcomes in defining PTEN status by immunohistochemistry.
Competing Interests: Declarations. Ethics approval: This study was conducted under institutional ethics approval. Conflict of interest: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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