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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State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_73E30C0132C1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
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.
Journal
Journal of thoracic oncology
ISSN
1556-1380 (Electronic)
ISSN-L
1556-0864
Publication state
Published
Issued date
12/2018
Peer-reviewed
Oui
Volume
13
Number
12
Pages
1851-1863
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
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.
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.
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.
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.
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.
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.
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.
Keywords
Adenocarcinoma of Lung/metabolism, Adenocarcinoma of Lung/pathology, Adenocarcinoma of Lung/surgery, Aged, Biomarkers, Tumor, 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, Cohort Studies, Diagnosis, Computer-Assisted/methods, Female, Follow-Up Studies, Humans, Immunohistochemistry/methods, Lung Neoplasms/metabolism, Lung Neoplasms/pathology, Lung Neoplasms/surgery, Male, Middle Aged, PTEN Phosphohydrolase/metabolism, Pathologists/statistics & numerical data, Prognosis, Survival Rate, Tissue Array Analysis, Computer-based intensity measurement, External quality assessment, Immunohistochemistry, NSCLC, PTEN
Pubmed
Web of science
Open Access
Yes
Create date
29/10/2018 11:02
Last modification date
21/11/2022 9:23