Abstract

Aims: CD30 immunohistochemistry (IHC) in malignant lymphoma is used for selection of patients in clinical trials using brentuximab vedotin, an antibody drug-conjugate targeting the CD30 molecule. For reliable implementation in daily practice and meaningful selection of patients for clinical trials, information on technical variation and interobserver reproducibility of CD30 immunohistochemistry (IHC) staining is required. Methods and results: We conducted a three-round reproducibility assessment of CD30 scoring for categorised frequency and intensity, including a technical validation, a ‘live polling’ pre- and post-instruction scoring round and a web-based round including individual scoring with additional IHC information to mimic daily diagnostic practice. Agreement in all three scoring rounds was poor to fair (κ = 0.12–0.35 for CD30-positive tumour cell percentage and κ = 0.16–0.41 for staining intensity), even when allowing for one category of freedom in percentage of tumour cell positivity (κ = 0.30–0.61). The first round with CD30 staining performed in five independent laboratories showed objective differences in staining intensity. In the second round, approximately half the pathologists changed their opinion on CD30 frequency after a discussion on potential pitfalls, highlighting hesitancy in decision-making. Using fictional cut-off points for percentage of tumour cell positivity, agreement was still suboptimal (κ = 0.35–0.60). Conclusions: Lack of agreement in cases with heterogeneous expression is shown to influence patient eligibility for treatment with brentuximab vedotin, both in clinical practice and within the context of clinical trials, and limits the potential predictive value of the relative frequency of CD30-positive neoplastic cells for clinical response.

Original languageEnglish
Pages (from-to)473-482
Number of pages10
JournalHistopathology
Volume73
Issue number3
DOIs
Publication statusPublished - 1 Sep 2018

Cite this

@article{bd31ab34c9764f32987e50bb49a93fec,
title = "Interobserver variation in CD30 immunohistochemistry interpretation; consequences for patient selection for targeted treatment",
abstract = "Aims: CD30 immunohistochemistry (IHC) in malignant lymphoma is used for selection of patients in clinical trials using brentuximab vedotin, an antibody drug-conjugate targeting the CD30 molecule. For reliable implementation in daily practice and meaningful selection of patients for clinical trials, information on technical variation and interobserver reproducibility of CD30 immunohistochemistry (IHC) staining is required. Methods and results: We conducted a three-round reproducibility assessment of CD30 scoring for categorised frequency and intensity, including a technical validation, a ‘live polling’ pre- and post-instruction scoring round and a web-based round including individual scoring with additional IHC information to mimic daily diagnostic practice. Agreement in all three scoring rounds was poor to fair (κ = 0.12–0.35 for CD30-positive tumour cell percentage and κ = 0.16–0.41 for staining intensity), even when allowing for one category of freedom in percentage of tumour cell positivity (κ = 0.30–0.61). The first round with CD30 staining performed in five independent laboratories showed objective differences in staining intensity. In the second round, approximately half the pathologists changed their opinion on CD30 frequency after a discussion on potential pitfalls, highlighting hesitancy in decision-making. Using fictional cut-off points for percentage of tumour cell positivity, agreement was still suboptimal (κ = 0.35–0.60). Conclusions: Lack of agreement in cases with heterogeneous expression is shown to influence patient eligibility for treatment with brentuximab vedotin, both in clinical practice and within the context of clinical trials, and limits the potential predictive value of the relative frequency of CD30-positive neoplastic cells for clinical response.",
keywords = "CD30, immunohistochemistry, interobserver variation, malignant lymphoma",
author = "Lianne Koens and {van de Ven}, {Peter M.} and Hijmering, {Nathalie J.} and Kersten, {Marie J.} and Arjan Diepstra and Martine Chamuleau and {de Jong}, Daphne",
year = "2018",
month = "9",
day = "1",
doi = "10.1111/his.13647",
language = "English",
volume = "73",
pages = "473--482",
journal = "Histopathology",
issn = "0309-0167",
publisher = "Wiley-Blackwell",
number = "3",

}

Interobserver variation in CD30 immunohistochemistry interpretation; consequences for patient selection for targeted treatment. / Koens, Lianne; van de Ven, Peter M.; Hijmering, Nathalie J.; Kersten, Marie J.; Diepstra, Arjan; Chamuleau, Martine; de Jong, Daphne.

In: Histopathology, Vol. 73, No. 3, 01.09.2018, p. 473-482.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Interobserver variation in CD30 immunohistochemistry interpretation; consequences for patient selection for targeted treatment

AU - Koens, Lianne

AU - van de Ven, Peter M.

AU - Hijmering, Nathalie J.

AU - Kersten, Marie J.

AU - Diepstra, Arjan

AU - Chamuleau, Martine

AU - de Jong, Daphne

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Aims: CD30 immunohistochemistry (IHC) in malignant lymphoma is used for selection of patients in clinical trials using brentuximab vedotin, an antibody drug-conjugate targeting the CD30 molecule. For reliable implementation in daily practice and meaningful selection of patients for clinical trials, information on technical variation and interobserver reproducibility of CD30 immunohistochemistry (IHC) staining is required. Methods and results: We conducted a three-round reproducibility assessment of CD30 scoring for categorised frequency and intensity, including a technical validation, a ‘live polling’ pre- and post-instruction scoring round and a web-based round including individual scoring with additional IHC information to mimic daily diagnostic practice. Agreement in all three scoring rounds was poor to fair (κ = 0.12–0.35 for CD30-positive tumour cell percentage and κ = 0.16–0.41 for staining intensity), even when allowing for one category of freedom in percentage of tumour cell positivity (κ = 0.30–0.61). The first round with CD30 staining performed in five independent laboratories showed objective differences in staining intensity. In the second round, approximately half the pathologists changed their opinion on CD30 frequency after a discussion on potential pitfalls, highlighting hesitancy in decision-making. Using fictional cut-off points for percentage of tumour cell positivity, agreement was still suboptimal (κ = 0.35–0.60). Conclusions: Lack of agreement in cases with heterogeneous expression is shown to influence patient eligibility for treatment with brentuximab vedotin, both in clinical practice and within the context of clinical trials, and limits the potential predictive value of the relative frequency of CD30-positive neoplastic cells for clinical response.

AB - Aims: CD30 immunohistochemistry (IHC) in malignant lymphoma is used for selection of patients in clinical trials using brentuximab vedotin, an antibody drug-conjugate targeting the CD30 molecule. For reliable implementation in daily practice and meaningful selection of patients for clinical trials, information on technical variation and interobserver reproducibility of CD30 immunohistochemistry (IHC) staining is required. Methods and results: We conducted a three-round reproducibility assessment of CD30 scoring for categorised frequency and intensity, including a technical validation, a ‘live polling’ pre- and post-instruction scoring round and a web-based round including individual scoring with additional IHC information to mimic daily diagnostic practice. Agreement in all three scoring rounds was poor to fair (κ = 0.12–0.35 for CD30-positive tumour cell percentage and κ = 0.16–0.41 for staining intensity), even when allowing for one category of freedom in percentage of tumour cell positivity (κ = 0.30–0.61). The first round with CD30 staining performed in five independent laboratories showed objective differences in staining intensity. In the second round, approximately half the pathologists changed their opinion on CD30 frequency after a discussion on potential pitfalls, highlighting hesitancy in decision-making. Using fictional cut-off points for percentage of tumour cell positivity, agreement was still suboptimal (κ = 0.35–0.60). Conclusions: Lack of agreement in cases with heterogeneous expression is shown to influence patient eligibility for treatment with brentuximab vedotin, both in clinical practice and within the context of clinical trials, and limits the potential predictive value of the relative frequency of CD30-positive neoplastic cells for clinical response.

KW - CD30

KW - immunohistochemistry

KW - interobserver variation

KW - malignant lymphoma

UR - http://www.scopus.com/inward/record.url?scp=85051419487&partnerID=8YFLogxK

U2 - 10.1111/his.13647

DO - 10.1111/his.13647

M3 - Article

VL - 73

SP - 473

EP - 482

JO - Histopathology

JF - Histopathology

SN - 0309-0167

IS - 3

ER -