Header

UZH-Logo

Maintenance Infos

Computer-based intensity measurement assists pathologists in scoring PTEN immunohistochemistry - Clinical associations in NSCLC patients of the ETOP Lungscape cohort


Abstract

INTRODUCTION PTEN loss is frequently observed in NSCLC and associated with both PI3K activation and tumoral immunosuppression. PTEN immunohistochemistry is a valuable read-out, but lacks standardized staining protocol and cut-off value. METHODS Following an external quality assessment (EQA) using SP218, 138G6 and 6H2.1 anti-PTEN antibodies, scored on webbook and tissue microarray, the ETOP cohort samples (n=2245 NSCLC patients, 8980 TMA cores) were stained with SP218. All cores were H-scored by pathologists and by computerized pixel-based intensity measurements calibrated by pathologists. RESULTS All 3 antibodies differentiated 6 PTEN+ versus 6 PTEN- cases on EQA. 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. Due to over-integration of the human eye, pixel-based computer H-scores were overall 54% lower. For all cut-off 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 multi-centre studies.

Abstract

INTRODUCTION PTEN loss is frequently observed in NSCLC and associated with both PI3K activation and tumoral immunosuppression. PTEN immunohistochemistry is a valuable read-out, but lacks standardized staining protocol and cut-off value. METHODS Following an external quality assessment (EQA) using SP218, 138G6 and 6H2.1 anti-PTEN antibodies, scored on webbook and tissue microarray, the ETOP cohort samples (n=2245 NSCLC patients, 8980 TMA cores) were stained with SP218. All cores were H-scored by pathologists and by computerized pixel-based intensity measurements calibrated by pathologists. RESULTS All 3 antibodies differentiated 6 PTEN+ versus 6 PTEN- cases on EQA. 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. Due to over-integration of the human eye, pixel-based computer H-scores were overall 54% lower. For all cut-off 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 multi-centre studies.

Statistics

Citations

Dimensions.ai Metrics

Altmetrics

Downloads

48 downloads since deposited on 26 Oct 2018
47 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology and Hematology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Thoracic Surgery
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:1 December 2018
Deposited On:26 Oct 2018 10:57
Last Modified:26 Oct 2019 07:05
Publisher:Elsevier
ISSN:1556-0864
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.jtho.2018.08.2034
PubMed ID:30240851

Download

Green Open Access

Download PDF  'Computer-based intensity measurement assists pathologists in scoring PTEN immunohistochemistry - Clinical associations in NSCLC patients of the ETOP Lungscape cohort'.
Preview
Content: Accepted Version
Filetype: PDF
Size: 2MB
View at publisher
Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Download PDF  'Computer-based intensity measurement assists pathologists in scoring PTEN immunohistochemistry - Clinical associations in NSCLC patients of the ETOP Lungscape cohort'.
Preview
Content: Published Version
Filetype: PDF
Size: 2MB
Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)