TY - JOUR
TI - 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, U.
AU - Tsourti, Z.
AU - Casanova, R.
AU - Deml, K.-F.
AU - Verbeken, E.
AU - Thunnissen, E.
AU - Warth, A.
AU - Cheney, R.
AU - Sejda, A.
AU - Speel, E.J.
AU - Madsen, L.B.
AU - Nonaka, D.
AU - Navarro, A.
AU - Sansano, I.
AU - Marchetti, A.
AU - Finn, S.P.
AU - Monkhorst, K.
AU - Kerr, K.M.
AU - Haberecker, M.
AU - Wu, C.
AU - Zygoura, P.
AU - Kammler, R.
AU - Geiger, T.
AU - Gendreau, S.
AU - Schulze, K.
AU - Vrugt, B.
AU - Wild, P.
AU - Moch, H.
AU - Weder, W.
AU - Ciftlik, A.T.
AU - Dafni, U.
AU - Peters, S.
AU - Bubendorf, L.
AU - Stahel, R.A.
AU - Soltermann, A.
JO - Journal of Thoracic Oncology
PY - 2018
VL - 13
TODO - 12
SP - 1851-1863
PB - HANLEY & BELFUS-ELSEVIER INC
SN - 1556-0864, 1556-1380
TODO - 10.1016/j.jtho.2018.08.2034
TODO - B Raf kinase;  epidermal growth factor receptor;  K ras protein;  phosphatidylinositol 3 kinase;  phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase;  scatter factor receptor;  tyrosine kinase receptor;  phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase;  PTEN protein, human;  tumor marker, adult;  aged;  Article;  BRAF gene;  cancer mortality;  cancer prognosis;  cancer staging;  cancer survival;  controlled study;  EGFR gene;  female;  fluorescence in situ hybridization;  histology;  human;  human tissue;  immunohistochemistry;  immunoreactivity;  KRAS gene;  major clinical study;  male;  median survival time;  mortality risk;  mRNA expression level;  non small cell lung cancer;  overall survival;  PIK3CA gene;  prevalence;  priority journal;  prospective study;  protein expression;  receiver operating characteristic;  recurrence free survival;  sensitivity and specificity;  smoking;  tissue microarray;  tumor volume;  cohort analysis;  computer assisted diagnosis;  follow up;  immunohistochemistry;  large cell carcinoma;  lung adenocarcinoma;  lung tumor;  metabolism;  middle aged;  non small cell lung cancer;  pathologist;  pathology;  procedures;  prognosis;  squamous cell carcinoma;  survival rate, Adenocarcinoma of Lung;  Aged;  Biomarkers, Tumor;  Carcinoma, Large Cell;  Carcinoma, Non-Small-Cell Lung;  Carcinoma, Squamous Cell;  Cohort Studies;  Diagnosis, Computer-Assisted;  Female;  Follow-Up Studies;  Humans;  Immunohistochemistry;  Lung Neoplasms;  Male;  Middle Aged;  Pathologists;  Prognosis;  PTEN Phosphohydrolase;  Survival Rate;  Tissue Array Analysis
TODO - 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. © 2018 International Association for the Study of Lung Cancer
ER -