1. Computer-Based Intensity Measurement Assists Pathologists in Scoring Phosphatase and Tensin Homolog Immunohistochemistry - Clinical Associations in NSCLC Patients of the European Thoracic Oncology Platform Lungscape Cohort
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Steven Gendreau, Martina Haberecker, Ata Tuna Ciftlik, Keith M. Kerr, Roswitha Kammler, Solange Peters, Richard Cheney, Kim Monkhorst, Karl-Friedrich Deml, Undine Rulle, Ruben Casanova, Irene Sansano, Bart Vrugt, Zoi Tsourti, Ernst-Jan M. Speel, Chengguang Wu, Rolf A. Stahel, Eric Verbeken, Antonio Marchetti, Urania Dafni, Thomas Geiger, Peter J. Wild, Walter Weder, Lukas Bubendorf, Arne Warth, Line Bille Madsen, Atilio Navarro, Panagiota Zygoura, Aleksandra Sejda, Holger Moch, Katja Schulze, Daisuke Nonaka, Erik Thunnissen, Alex Soltermann, Stephen P. Finn, RS: GROW - R2 - Basic and Translational Cancer Biology, Pathologie, CCA - Cancer Treatment and quality of life, and Pathology
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0301 basic medicine ,Oncology ,Male ,PTEN ,Lung Neoplasms ,Computer-based intensity measurement ,Respiratory System ,NSCLC ,Cohort Studies ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,ENDOMETRIAL CARCINOMA ,ANALYTIC VALIDATION ,Tensin ,Diagnosis, Computer-Assisted ,HER2 IMMUNOHISTOCHEMISTRY ,Tissue microarray ,biology ,Middle Aged ,Prognosis ,Immunohistochemistry ,External quality assessment ,PROSTATE-CANCER ,Survival Rate ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Biomarker (medicine) ,Female ,SQUAMOUS-CELL CARCINOMA ,Life Sciences & Biomedicine ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Concordance ,Adenocarcinoma of Lung ,BREAST ,03 medical and health sciences ,LUNG-CANCER ,Thoracic Oncology ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,DEREGULATION ,TISSUE MICROARRAY ,Aged ,Science & Technology ,business.industry ,PTEN Phosphohydrolase ,Histology ,Pathologists ,030104 developmental biology ,Tissue Array Analysis ,PTEN EXPRESSION ,biology.protein ,Carcinoma, Large Cell ,business ,Adenocarcinoma of Lung/metabolism ,Adenocarcinoma of Lung/pathology ,Adenocarcinoma of Lung/surgery ,Carcinoma, Large Cell/metabolism ,Carcinoma, Large Cell/pathology ,Carcinoma, Large Cell/surgery ,Carcinoma, Non-Small-Cell Lung/metabolism ,Carcinoma, Non-Small-Cell Lung/pathology ,Carcinoma, Non-Small-Cell Lung/surgery ,Carcinoma, Squamous Cell/metabolism ,Carcinoma, Squamous Cell/pathology ,Carcinoma, Squamous Cell/surgery ,Diagnosis, Computer-Assisted/methods ,Follow-Up Studies ,Immunohistochemistry/methods ,Lung Neoplasms/metabolism ,Lung Neoplasms/pathology ,Lung Neoplasms/surgery ,PTEN Phosphohydrolase/metabolism ,Pathologists/statistics & numerical data - Abstract
Introduction: Phosphatase and tensin homolog (PTEN) loss is frequently observed in NSCLC and associated with both phosphoinositide 3-kinase activation and tumoral immunosuppression. PTEN immunohistochemistry is a valuable readout, but lacks standardized staining protocol and cutoff value. Methods: After an external quality assessment using SP218, 138G6 and 6H2.1 anti-PTEN antibodies, scored on webbook and tissue microarray, the European Thoracic Oncology Platform cohort samples (n = 2245 NSCLC patients, 8980 tissue microarray cores) were stained with SP218. All cores were H-scored by pathologists and by computerized pixel-based intensity measurements calibrated by pathologists. Results: All three antibodies differentiated six PTEN+ versus six PTEN- cases on external quality assessment. For 138G6 and SP218, high sensitivity and specificity was found for all H-score threshold values including prospectively defined 0, calculated 8 (pathologists), and calculated 5 (computer). High concordance among pathologists in setting computer-based intensities and between pathologists and computer in H-scoring was observed. Because of over-integration of the human eye, pixel-based computer H-scores were overall 54% lower. For all cutoff values, PTEN-was associated with smoking history, squamous cell histology, and higher tumor stage (p < 0.001). In adenocarcinomas, PTEN-was associated with poor survival. Conclusion: Calibration of immunoreactivity intensities by pathologists following computerized H-score measurements has the potential to improve reproducibility and homogeneity of biomarker detection regarding epitope validation in multicenter studies. (C) 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
- Published
- 2018
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