Challenging pathologist`s eye with computer-based intensity measurement in PTEN immunohistochemistry
Undine Rulle1, Ruben Casanova1, Zoi Tsourti2, Arne Warth3, Maria Calabuig4, Eric Verbeken5, Aleksandra Sejda6, Rosita Kammler7, Lukas Bubendorf8, Lungscape Consortium9, Alex Soltermann1
1 Department of Pathology University Hospital Zurich, Zurich, Switzerland
2 ETOP Statistical Center Frontier Science Foundation Hellas, Athens, Greece
3 Department of Pathology, University Clinic Heidelberg, Heidelberg, Germany
4 Department of Pathology, Hospital General University Valencia, Valencia, Spain
5 Department of Pathology, University Hospital Leuven, Leuven, Belgium
6 Department of Pathology, Medical University of Gdansk, Poland
7 Translational Research Coordination, ETOP Coordinating Center, Bern, Switzerland
8 Institute of Pahology, University Hospital Basel, Basel, Switzerland9 European Thoracic Oncology Platform (ETOP) Lungscape participating sites, steering committee, central offices.
Background PTEN is a tumour suppressor that serves as surrogate biomarker for PI3KAkt pathway, indicating tumours that would respond to treatment.
Methods For external quality assessment (EQA), different type of cancer tissues (n=12, FFPE sections) were stained for PTEN using 3 antibodies SP218, 138G6, 6H2.1 and scored by pathologist and computer method in order to determine the antibody and scoring threshold. We then performed PTEN on the ETOP cohort including 2245 patients from non-small cell lung cancer (NSCLC).
Results Using EQA PTEN loss was define as H-score = 0. In full cohort PTEN loss was detected in 981 patients (43.7%) and was significantly associated with male sex (47.2% vs 36.9%), smoking history (24.5% never smokers vs 46.5% in smokers), histology (37.4% adenocarcinoma vs 51.2% squamous cell carcinoma), stage (40.4%, 45.5%, 48.3% for stage I, II, III) and tumour size (4.0 cm vs 3.4 cm). Further it was significantly associated with poor overall survival (OS) in adenocarcinoma (HR=1.20). Computer and pathologists scores were comparable- computer H-scores had lower averages and lower inter-centre variability.
Conclusion PTEN loss is strongly associated with advanced disease and adenocarcinoma histology. Computerized immunoreactivity measurements are a promising alternative to pathologists’ scorings.