The impact of a pathologist's personality on the interobserver variability and diagnostic accuracy of predictive PD-L1 immunohistochemistry in lung cancer

Rogier Butter; Liesbeth M Hondelink; Lisette van Elswijk; Johannes L G Blaauwgeers; Elisabeth Bloemena; Rieneke Britstra; Nicole Bulkmans; Anna Lena van Gulik; Kim Monkhorst; Mathilda J de Rooij; Ivana Slavujevic-Letic; Vincent T H B M Smit; Ernst-Jan M Speel; Erik Thunnissen; Jan H von der Thüsen; Wim Timens; Marc J van de Vijver; David C Y Yick; Aeilko H Zwinderman; Danielle Cohen; Nils A 't Hart; Teodora Radonic

doi:10.1016/j.lungcan.2022.03.002

The impact of a pathologist's personality on the interobserver variability and diagnostic accuracy of predictive PD-L1 immunohistochemistry in lung cancer

Rogier Butter, Liesbeth M Hondelink, Lisette van Elswijk, Johannes L G Blaauwgeers, Elisabeth Bloemena, Rieneke Britstra, Nicole Bulkmans, Anna Lena van Gulik, Kim Monkhorst, Mathilda J de Rooij, Ivana Slavujevic-Letic, Vincent T H B M Smit, Ernst-Jan M Speel, Erik Thunnissen, Jan H von der Thüsen, Wim Timens, Marc J van de Vijver, David C Y Yick, Aeilko H Zwinderman, Danielle CohenNils A 't Hart, Teodora Radonic^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

OBJECTIVES: Programmed death-ligand 1 (PD-L1) is the only approved predictive biomarker for immunotherapy in non-small cell lung cancer (NSCLC). However, predictive PD-L1 immunohistochemistry is subject to interobserver variability. We hypothesized that a pathologist's personality influences the interobserver variability and diagnostic accuracy of PD-L1 immunoscoring.

MATERIALS AND METHODS: Seventeen pathologists performed PD-L1 immunoscoring on 50 resected NSCLC tumors in three categories (<1%;1-49%;≥50%). Also, the pathologists completed a certified personality test (NEO-PI-r), assessing five personality traits: neuroticism, extraversion, openness, altruism and conscientiousness.

RESULTS: The overall agreement among pathologists for a series of 47 tumors was substantial (kappa = 0.63). Of these, 23/47 (49%) tumors were entirely negative or largely positive, resulting in a kappa value of 0.93. The remaining 24/47 (51%) tumors had a PD-L1 score around the cutoff value, generating a kappa value of 0.32. Pathologists with high scores for conscientiousness (careful, diligent) had the least interobserver variability (r = 0.6, p = 0.009). Also, they showed a trend towards higher sensitivity (74% vs. 68%, p = 0.4), specificity (86% vs. 82%, p = 0.3) and percent agreement (83% vs. 79%, p = 0.3), although not significant. In contrast, pathologists with high scores for neuroticism (sensitive, anxious) had significantly lower specificity (80% vs. 87%, p = 0.03) and percent agreement (78% vs. 85%, p = 0.03). Also, a trend towards high interobserver variability (r = -0.3, p = 0.2) and lower sensitivity (68% vs. 74%, p = 0.3) was observed, although not significant. Pathologists with relatively high scores for conscientiousness scored fewer tumors PD-L1 positive at the ≥ 1% cut-off (r = -0.5, p = 0.03). In contrast, pathologists with relatively high scores for neuroticism score more tumors PD-L1 positive at ≥ 1% (r = 0.6, p = 0.017) and ≥ 50% cut-offs (r = 0.6, p = 0.009).

CONCLUSIONS: This study is the first to demonstrate the impact of a pathologist's personality on the interobserver variability and diagnostic accuracy of immunostaining, in the context of PD-L1 in NSCLC. Larger studies are needed for validation of these findings.

Original language	English
Pages (from-to)	143-149
Number of pages	7
Journal	Lung Cancer
Volume	166
Early online date	5 Mar 2022
DOIs	https://doi.org/10.1016/j.lungcan.2022.03.002
Publication status	Published - Apr 2022

Keywords

CELL
DECISION-MAKING
Diagnostic reliability
EXPRESSION
Immunohistochemistry
Interobserver variability
Non-small cell lung cancer (NSCLC)
PEMBROLIZUMAB
TRAITS
programmed death-ligand 1 (PD-L1)

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Butter, R., Hondelink, L. M., van Elswijk, L., Blaauwgeers, J. L. G., Bloemena, E., Britstra, R., Bulkmans, N., van Gulik, A. L., Monkhorst, K., de Rooij, M. J., Slavujevic-Letic, I., Smit, V. T. H. B. M., Speel, E.-J. M., Thunnissen, E., von der Thüsen, J. H., Timens, W., van de Vijver, M. J., Yick, D. C. Y., Zwinderman, A. H., ... Radonic, T. (2022). The impact of a pathologist's personality on the interobserver variability and diagnostic accuracy of predictive PD-L1 immunohistochemistry in lung cancer. Lung Cancer, 166, 143-149. https://doi.org/10.1016/j.lungcan.2022.03.002

@article{7de8d4df5fce45c5a3f25bc4caff417e,

title = "The impact of a pathologist's personality on the interobserver variability and diagnostic accuracy of predictive PD-L1 immunohistochemistry in lung cancer",

abstract = "OBJECTIVES: Programmed death-ligand 1 (PD-L1) is the only approved predictive biomarker for immunotherapy in non-small cell lung cancer (NSCLC). However, predictive PD-L1 immunohistochemistry is subject to interobserver variability. We hypothesized that a pathologist's personality influences the interobserver variability and diagnostic accuracy of PD-L1 immunoscoring.MATERIALS AND METHODS: Seventeen pathologists performed PD-L1 immunoscoring on 50 resected NSCLC tumors in three categories (<1%;1-49%;≥50%). Also, the pathologists completed a certified personality test (NEO-PI-r), assessing five personality traits: neuroticism, extraversion, openness, altruism and conscientiousness.RESULTS: The overall agreement among pathologists for a series of 47 tumors was substantial (kappa = 0.63). Of these, 23/47 (49%) tumors were entirely negative or largely positive, resulting in a kappa value of 0.93. The remaining 24/47 (51%) tumors had a PD-L1 score around the cutoff value, generating a kappa value of 0.32. Pathologists with high scores for conscientiousness (careful, diligent) had the least interobserver variability (r = 0.6, p = 0.009). Also, they showed a trend towards higher sensitivity (74% vs. 68%, p = 0.4), specificity (86% vs. 82%, p = 0.3) and percent agreement (83% vs. 79%, p = 0.3), although not significant. In contrast, pathologists with high scores for neuroticism (sensitive, anxious) had significantly lower specificity (80% vs. 87%, p = 0.03) and percent agreement (78% vs. 85%, p = 0.03). Also, a trend towards high interobserver variability (r = -0.3, p = 0.2) and lower sensitivity (68% vs. 74%, p = 0.3) was observed, although not significant. Pathologists with relatively high scores for conscientiousness scored fewer tumors PD-L1 positive at the ≥ 1% cut-off (r = -0.5, p = 0.03). In contrast, pathologists with relatively high scores for neuroticism score more tumors PD-L1 positive at ≥ 1% (r = 0.6, p = 0.017) and ≥ 50% cut-offs (r = 0.6, p = 0.009).CONCLUSIONS: This study is the first to demonstrate the impact of a pathologist's personality on the interobserver variability and diagnostic accuracy of immunostaining, in the context of PD-L1 in NSCLC. Larger studies are needed for validation of these findings.",

keywords = "CELL, DECISION-MAKING, Diagnostic reliability, EXPRESSION, Immunohistochemistry, Interobserver variability, Non-small cell lung cancer (NSCLC), PEMBROLIZUMAB, TRAITS, programmed death-ligand 1 (PD-L1)",

author = "Rogier Butter and Hondelink, {Liesbeth M} and {van Elswijk}, Lisette and Blaauwgeers, {Johannes L G} and Elisabeth Bloemena and Rieneke Britstra and Nicole Bulkmans and {van Gulik}, {Anna Lena} and Kim Monkhorst and {de Rooij}, {Mathilda J} and Ivana Slavujevic-Letic and Smit, {Vincent T H B M} and Speel, {Ernst-Jan M} and Erik Thunnissen and {von der Th{\"u}sen}, {Jan H} and Wim Timens and {van de Vijver}, {Marc J} and Yick, {David C Y} and Zwinderman, {Aeilko H} and Danielle Cohen and {'t Hart}, {Nils A} and Teodora Radonic",

year = "2022",

month = apr,

doi = "10.1016/j.lungcan.2022.03.002",

language = "English",

volume = "166",

pages = "143--149",

journal = "Lung Cancer",

issn = "0169-5002",

publisher = "Elsevier Ireland Ltd",

}

Butter, R, Hondelink, LM, van Elswijk, L, Blaauwgeers, JLG, Bloemena, E, Britstra, R, Bulkmans, N, van Gulik, AL, Monkhorst, K, de Rooij, MJ, Slavujevic-Letic, I, Smit, VTHBM, Speel, E-JM, Thunnissen, E, von der Thüsen, JH, Timens, W, van de Vijver, MJ, Yick, DCY, Zwinderman, AH, Cohen, D, 't Hart, NA & Radonic, T 2022, 'The impact of a pathologist's personality on the interobserver variability and diagnostic accuracy of predictive PD-L1 immunohistochemistry in lung cancer', Lung Cancer, vol. 166, pp. 143-149. https://doi.org/10.1016/j.lungcan.2022.03.002

TY - JOUR

T1 - The impact of a pathologist's personality on the interobserver variability and diagnostic accuracy of predictive PD-L1 immunohistochemistry in lung cancer

AU - Butter, Rogier

AU - Hondelink, Liesbeth M

AU - van Elswijk, Lisette

AU - Blaauwgeers, Johannes L G

AU - Bloemena, Elisabeth

AU - Britstra, Rieneke

AU - Bulkmans, Nicole

AU - van Gulik, Anna Lena

AU - Monkhorst, Kim

AU - de Rooij, Mathilda J

AU - Slavujevic-Letic, Ivana

AU - Smit, Vincent T H B M

AU - Speel, Ernst-Jan M

AU - Thunnissen, Erik

AU - von der Thüsen, Jan H

AU - Timens, Wim

AU - van de Vijver, Marc J

AU - Yick, David C Y

AU - Zwinderman, Aeilko H

AU - Cohen, Danielle

AU - 't Hart, Nils A

AU - Radonic, Teodora

PY - 2022/4

Y1 - 2022/4

N2 - OBJECTIVES: Programmed death-ligand 1 (PD-L1) is the only approved predictive biomarker for immunotherapy in non-small cell lung cancer (NSCLC). However, predictive PD-L1 immunohistochemistry is subject to interobserver variability. We hypothesized that a pathologist's personality influences the interobserver variability and diagnostic accuracy of PD-L1 immunoscoring.MATERIALS AND METHODS: Seventeen pathologists performed PD-L1 immunoscoring on 50 resected NSCLC tumors in three categories (<1%;1-49%;≥50%). Also, the pathologists completed a certified personality test (NEO-PI-r), assessing five personality traits: neuroticism, extraversion, openness, altruism and conscientiousness.RESULTS: The overall agreement among pathologists for a series of 47 tumors was substantial (kappa = 0.63). Of these, 23/47 (49%) tumors were entirely negative or largely positive, resulting in a kappa value of 0.93. The remaining 24/47 (51%) tumors had a PD-L1 score around the cutoff value, generating a kappa value of 0.32. Pathologists with high scores for conscientiousness (careful, diligent) had the least interobserver variability (r = 0.6, p = 0.009). Also, they showed a trend towards higher sensitivity (74% vs. 68%, p = 0.4), specificity (86% vs. 82%, p = 0.3) and percent agreement (83% vs. 79%, p = 0.3), although not significant. In contrast, pathologists with high scores for neuroticism (sensitive, anxious) had significantly lower specificity (80% vs. 87%, p = 0.03) and percent agreement (78% vs. 85%, p = 0.03). Also, a trend towards high interobserver variability (r = -0.3, p = 0.2) and lower sensitivity (68% vs. 74%, p = 0.3) was observed, although not significant. Pathologists with relatively high scores for conscientiousness scored fewer tumors PD-L1 positive at the ≥ 1% cut-off (r = -0.5, p = 0.03). In contrast, pathologists with relatively high scores for neuroticism score more tumors PD-L1 positive at ≥ 1% (r = 0.6, p = 0.017) and ≥ 50% cut-offs (r = 0.6, p = 0.009).CONCLUSIONS: This study is the first to demonstrate the impact of a pathologist's personality on the interobserver variability and diagnostic accuracy of immunostaining, in the context of PD-L1 in NSCLC. Larger studies are needed for validation of these findings.

AB - OBJECTIVES: Programmed death-ligand 1 (PD-L1) is the only approved predictive biomarker for immunotherapy in non-small cell lung cancer (NSCLC). However, predictive PD-L1 immunohistochemistry is subject to interobserver variability. We hypothesized that a pathologist's personality influences the interobserver variability and diagnostic accuracy of PD-L1 immunoscoring.MATERIALS AND METHODS: Seventeen pathologists performed PD-L1 immunoscoring on 50 resected NSCLC tumors in three categories (<1%;1-49%;≥50%). Also, the pathologists completed a certified personality test (NEO-PI-r), assessing five personality traits: neuroticism, extraversion, openness, altruism and conscientiousness.RESULTS: The overall agreement among pathologists for a series of 47 tumors was substantial (kappa = 0.63). Of these, 23/47 (49%) tumors were entirely negative or largely positive, resulting in a kappa value of 0.93. The remaining 24/47 (51%) tumors had a PD-L1 score around the cutoff value, generating a kappa value of 0.32. Pathologists with high scores for conscientiousness (careful, diligent) had the least interobserver variability (r = 0.6, p = 0.009). Also, they showed a trend towards higher sensitivity (74% vs. 68%, p = 0.4), specificity (86% vs. 82%, p = 0.3) and percent agreement (83% vs. 79%, p = 0.3), although not significant. In contrast, pathologists with high scores for neuroticism (sensitive, anxious) had significantly lower specificity (80% vs. 87%, p = 0.03) and percent agreement (78% vs. 85%, p = 0.03). Also, a trend towards high interobserver variability (r = -0.3, p = 0.2) and lower sensitivity (68% vs. 74%, p = 0.3) was observed, although not significant. Pathologists with relatively high scores for conscientiousness scored fewer tumors PD-L1 positive at the ≥ 1% cut-off (r = -0.5, p = 0.03). In contrast, pathologists with relatively high scores for neuroticism score more tumors PD-L1 positive at ≥ 1% (r = 0.6, p = 0.017) and ≥ 50% cut-offs (r = 0.6, p = 0.009).CONCLUSIONS: This study is the first to demonstrate the impact of a pathologist's personality on the interobserver variability and diagnostic accuracy of immunostaining, in the context of PD-L1 in NSCLC. Larger studies are needed for validation of these findings.

KW - CELL

KW - DECISION-MAKING

KW - Diagnostic reliability

KW - EXPRESSION

KW - Immunohistochemistry

KW - Interobserver variability

KW - Non-small cell lung cancer (NSCLC)

KW - PEMBROLIZUMAB

KW - TRAITS

KW - programmed death-ligand 1 (PD-L1)

U2 - 10.1016/j.lungcan.2022.03.002

DO - 10.1016/j.lungcan.2022.03.002

M3 - Article

C2 - 35279453

SN - 0169-5002

VL - 166

SP - 143

EP - 149

JO - Lung Cancer

JF - Lung Cancer

ER -