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 - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85051419487&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29758590
UR - http://www.scopus.com/inward/record.url?scp=85051419487&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/his.13647
DO - https://doi.org/10.1111/his.13647
M3 - Article
C2 - 29758590
SN - 0309-0167
VL - 73
SP - 473
EP - 482
JO - Histopathology
JF - Histopathology
IS - 3
ER -