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
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
Author(s)
Rulle U., Tsourti Z., Casanova R., Deml K.F., Verbeken E., Thunnissen E., Warth A., Sejda A., Cheney R., 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.
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
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.
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 10:02
Last modification date
03/10/2019 5:09
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