Immunohistochemistry and Next Generation Sequencing are Complementary Tests in Identifying PTEN Abnormality in Endometrial Carcinoma Biopsies
Abstract
Summary PTEN plays a central role in the pathogenesis of endometrial carcinoma. Previous studies reported a high interobserver reproducibility for the interpretation of PTEN immunohistochemistry (IHC). However, PTEN IHC and its interpretation remain challenging during laboratory practice. The purpose of this study was to reevaluate PTEN IHC pattern in direct comparison to next generation sequencing (NGS) in identifying PTEN abnormality. IHC and tagged-amplicon NGS PTEN sequencing was performed on 182 endometrial carcinoma biopsy/curetting samples from five centers (Barts, Calgary, Cambridge, Leiden, and Vancouver). Sensitivity, specificity and accuracy of PTEN IHC to predict loss of function (LOF) PTEN mutations were calculated. Abnormalities of PTEN in association with histotype and molecular subtype were assessed. A total of five PTEN IHC patterns were recorded: absent, subclonal loss, equivocal, reduced (relative to internal control) and retained. The absence of PTEN IHC has a sensitivity of 75.4% (95% CI 62.7 – 85.5%), a specificity of 84.6% (95% CI 76.2 – 90.9%), and accuracy of 81.2% (95% CI 74.4 – 86.9%) in predicting LOF PTEN mutation. PTEN abnormality by complementary interpretation of both assays was present in 91.9% of endometrial endometrioid carcinoma, grade 1, and significantly higher in endometrial endometrioid carcinomas of all grades compared to endometrial serous carcinoma (80.0% versus 19.4%, p<0.0001). PTEN abnormalities are common across all molecular subtypes of endometrioid carcinomas. Our data support complementary testing of both IHC and sequencing of PTEN to assess the PTEN status in endometrial carcinomas.
Authors 9
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Affiliation as printed
Department of Pathology, University of Calgary, Calgary, Alberta, Canada
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University of Cambridge · Cancer Research UK
Affiliation as printed
Cancer Research UK Cambridge Institute, University of Cambridge, UK
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Affiliation as printed
Department of Pathology, University of Leiden, Leiden, The Netherlands
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Affiliation as printed
Department of Pathology, Addenbrooke’s Hospital, Cambridge, UK
Department of Pathology, Addenbrooke's Hospital, Cambridge, UK
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Affiliation as printed
Department of Pathology, Addenbrooke’s Hospital, Cambridge, UK
Department of Pathology, Addenbrooke's Hospital, Cambridge, UK
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Affiliation as printed
Department of Pathology Vancouver General Hospital, Vancouver, British Columbia, Canada
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University of Cambridge · Cancer Research UK
Affiliation as printed
Cancer Research UK Cambridge Institute, University of Cambridge, UK
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Affiliation as printed
Department of Pathology, Barts Health NHS Trust, London, UK
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Martin Köbel corresponding
Affiliation as printed
Department of Pathology, University of Calgary, Calgary, Alberta, Canada
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