TY - JOUR
T1 - 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
AU - Rulle, Undine
AU - Tsourti, Zoi
AU - Casanova, Ruben
AU - Deml, Karl-Friedrich
AU - Verbeken, Eric
AU - Thunnissen, Erik
AU - Warth, Arne
AU - Cheney, Richard
AU - Sejda, Aleksandra
AU - Speel, Ernst Jan
AU - Madsen, Line Bille
AU - Nonaka, Daisuke
AU - Navarro, Atilio
AU - Sansano, Irene
AU - Marchetti, Antonio
AU - Finn, Stephen P.
AU - Monkhorst, Kim
AU - Kerr, Keith M.
AU - Haberecker, Martina
AU - Wu, Chengguang
AU - Zygoura, Panagiota
AU - Kammler, Roswitha
AU - Geiger, Thomas
AU - Gendreau, Steven
AU - Schulze, Katja
AU - Vrugt, Bart
AU - Wild, Peter
AU - Moch, Holger
AU - Weder, Walter
AU - Ciftlik, Ata Tuna
AU - Dafni, Urania
AU - Peters, Solange
AU - Bubendorf, Lukas
AU - Stahel, Rolf A.
AU - Soltermann, Alex
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85055263969&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30240851
U2 - 10.1016/j.jtho.2018.08.2034
DO - 10.1016/j.jtho.2018.08.2034
M3 - Article
C2 - 30240851
VL - 13
SP - 1851
EP - 1863
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
SN - 1556-0864
IS - 12
ER -