Τίτλος:
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
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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
Συγγραφείς:
Rulle, U.
Tsourti, Z.
Casanova, R.
Deml, K.-F.
Verbeken, E.
Thunnissen, E.
Warth, A.
Cheney, R.
Sejda, A.
Speel, E.J.
Madsen, L.B.
Nonaka, D.
Navarro, A.
Sansano, I.
Marchetti, A.
Finn, S.P.
Monkhorst, K.
Kerr, K.M.
Haberecker, M.
Wu, C.
Zygoura, P.
Kammler, R.
Geiger, T.
Gendreau, S.
Schulze, K.
Vrugt, B.
Wild, P.
Moch, H.
Weder, W.
Ciftlik, A.T.
Dafni, U.
Peters, S.
Bubendorf, L.
Stahel, R.A.
Soltermann, A.
Περιοδικό:
Journal of Thoracic Oncology
Εκδότης:
HANLEY & BELFUS-ELSEVIER INC
Λέξεις-κλειδιά:
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
DOI:
10.1016/j.jtho.2018.08.2034
