Interobserver Agreement of PD-L1/SP142 Immunohistochemistry and Tumor-Infiltrating Lymphocytes (TILs) in Distant Metastases of Triple-Negative Breast Cancer: A Proof-of-Concept Study. A Report on Behalf of the International Immuno-Oncology Biomarker Working Group

Bockstal, Mieke Van; Cooks, Maxine; Nederlof, Iris; Brinkhuis, Mariël; Dutman, Annemiek C.; Koopmans, Monique; Kooreman, Loes; Vegt, Bert van der; Verhoog, L.C.; Vreuls, Celine; Westenend, Pieter J.; Kok, Marleen; Diest, Paul J. van; Nauwelaers, Inne; Laudus, Nele; Denkert, Carsten; Rimm, David L.; Siziopikou, Kalliopi P.; Ely, Scott; Zardavas, Dimitrios; Roberts, Maegan E.; Floris, Giuseppe; Hartman, Johan; Ács, Balázs; Peeters, Dieter; Bartlett, John M.S.; Dequeker, Els; Salgado, Roberto; Giudici, Fabiola; Michiels, Stefan; Horlings, Hugo M.; Deurzen, Carolien H.M. van

doi:10.3390/cancers13194910

Cited by 11 publications

(9 citation statements)

References 52 publications

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“…Introducing a new scoring system without training might not reflect the true potential of the scoring system. 37,38 Although 2 different variables are combined to produce H-score (percent positive cells and staining intensity), our results showed that interobserver reliability was as good for H-score if not slightly superior to PPS, as shown by the statistical analysis. One explanation might be that differences between readers for low positive cases have a lesser impact on the total H-score than differences in strongly positive cases because the former percent is multiplied by 1 and the latter by 3.…”

Section: Discussionmentioning

confidence: 57%

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Reinventing Nuclear Histo-score Utilizing Inherent Morphologic Cutoffs: Blue-brown Color H-score (BBC-HS)

Price

Ganugapati

Gatalica

et al. 2023

Applied Immunohistochemistry &Amp; Molecular Morphology

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Immunohistochemistry (IHC) is a testing methodology that is widely used for large number of diagnostic, prognostic, and predictive biomarkers. Although IHC is a qualitative methodology, in addition to threshold-based stratification (positive vs. negative), the increasing levels of expression of some of these biomarkers often lead to more intense staining, which published evidence linked to specific diagnosis, prognosis, and responses to therapy. It is essential that the descriptive thresholds between positive and negative staining, as well as between frequently used graded categories of staining intensity (eg, 1+, 2+, 3+) are standardized and reproducible. Histo-score (H-score) is a frequently used scoring system that utilizes these categories. Our study introduces categorization of the cutoff points between positive and negative results and graded categories of staining intensity for nuclear IHC biomarker assays based on color interaction between hematoxylin and diaminobenzidine (DAB); the Blue-brown Color H-score (BBC-HS). Six cases of diffuse large B-cell lymphoma were stained for a nuclear marker MUM1. The staining was assessed by H-score by 12 readers. Short tutorial and illustrated instructions were provided to readers. The novel scoring system in this study uses the interaction between DAB (DAB, brown stain) and hematoxylin (blue counterstain) to set thresholds between “0” (negative nuclei), “1+” (weakly positive nuclei), “2+” (moderately positive nuclei), and “3+” (strongly positive nuclei). The readers recorded scores for 300 cells. Krippendorff alpha (K-alpha) and intraclass correlation coefficient (ICC) were calculated. We have also assessed if reliability improved when counting the first 100 cells, first 200 cells, and for the total 300 cells using K-alpha and ICC. To assess the performance of each individual reader, the mean H-score and percent positive score (PPS) for each case was calculated, and the bias was calculated between each reader’s score and the mean. K-alpha was 0.86 for H-score and 0.76 for PPS. ICC was 0.96 for H-score and 0.92 for PPS. The biases for H-score ranged from −58 to 41, whereas for PPS it ranged from −27% to 33%. Overall, most readers showed very low bias. Two readers were consistently underscoring and 2 were consistently overscoring compared with the mean. For nuclear IHC biomarker assays, our newly proposed cutoffs provide highly reliable/reproducible results between readers for positive and negative results and graded categories of staining intensity using existing morphologic parameters. BBC-HS is easy to teach and is applicable to both human eye and image analysis. BBC-HS application should facilitate the development of new reliable/reproducible scoring schemes for IHC biomarkers.

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Section: Discussionmentioning

confidence: 57%

“…In their study, however, there was no training for the readers. Introducing a new scoring system without training might not reflect the true potential of the scoring system 37,38 …”

Section: Discussionmentioning

confidence: 99%

Reinventing Nuclear Histo-score Utilizing Inherent Morphologic Cutoffs: Blue-brown Color H-score (BBC-HS)

Price

Ganugapati

Gatalica

et al. 2023

Applied Immunohistochemistry &Amp; Molecular Morphology

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“…Additionally, the necessity of proper training of pathologists in the assessment of PD-L1 with SP142 is emphasized, as there is a large discrepancy in the interpretation of results between pathologists, especially in samples from metastases [19].…”

Section: Qualification For Treatmentmentioning

confidence: 99%

Atezolizumab in the treatment of patients with breast cancer

Pogoda¹,

Jagiełło-Gruszfeld²,

Kunkiel³

et al. 2023

Oncol Clin Pract

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Immunotherapy is a modern method of treatment which is being tested in breast cancer patients. The first approved drug in this group was atezolizumab introduced for the treatment of patients with locally advanced and inoperable or metastatic triple-negative breast cancer (TNBC) with expression of programmed death receptor type 1 (PD-L1) on immunologic cells (IC) of ≥1%, who had not received prior chemotherapy for advanced disease. The results of the registration study IMpassion130 indicated that atezolizumab improved patient outcomes when used in combination with nab-paclitaxel. This article summarizes the most important analyzes of that study.The necessity to use the validated VENTANA SP142 assay to assess PD-L1 expression, which is necessary for the qualification of patients for this therapy, was emphasized. Additionally, the available data on the first results of the studies in patients with early TNBC as well as with human epidermal receptor type 2 (HER2)-positive and estrogen receptor (ER)-positive HER2-negative cancers treated with atezolizumab are discussed.

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“…In contrast, in the NeoTRIPaPDL1 trial, no difference in pCR rates was observed between the PD-L1-positive and the PD-L1-negative groups [ 83 ]. Again, these contradictory results might partly be explained by the relatively high degree of inter-observer variability among pathologists in PD-L1 immunohistochemical assessment, as reported for both primary and metastatic TNBC [ 84 , 85 ].…”

Section: Current Biomarkers Used For the Clinical Decision Making Of ...mentioning

confidence: 99%

Predictive Biomarkers of Response to Neoadjuvant Chemotherapy in Breast Cancer: Current and Future Perspectives for Precision Medicine

Derouane

Marcke

Berlière

et al. 2022

Cancers

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Pathological complete response (pCR) after neoadjuvant chemotherapy in patients with early breast cancer is correlated with better survival. Meanwhile, an expanding arsenal of post-neoadjuvant treatment strategies have proven beneficial in the absence of pCR, leading to an increased use of neoadjuvant systemic therapy in patients with early breast cancer and the search for predictive biomarkers of response. The better prediction of response to neoadjuvant chemotherapy could enable the escalation or de-escalation of neoadjuvant treatment strategies, with the ultimate goal of improving the clinical management of early breast cancer. Clinico-pathological prognostic factors are currently used to estimate the potential benefit of neoadjuvant systemic treatment but are not accurate enough to allow for personalized response prediction. Other factors have recently been proposed but are not yet implementable in daily clinical practice or remain of limited utility due to the intertumoral heterogeneity of breast cancer. In this review, we describe the current knowledge about predictive factors for response to neoadjuvant chemotherapy in breast cancer patients and highlight the future perspectives that could lead to the better prediction of response, focusing on the current biomarkers used for clinical decision making and the different gene signatures that have recently been proposed for patient stratification and the prediction of response to therapies. We also discuss the intratumoral phenotypic heterogeneity in breast cancers as well as the emerging techniques and relevant pre-clinical models that could integrate this biological factor currently limiting the reliable prediction of response to neoadjuvant systemic therapy.

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Interobserver Agreement of PD-L1/SP142 Immunohistochemistry and Tumor-Infiltrating Lymphocytes (TILs) in Distant Metastases of Triple-Negative Breast Cancer: A Proof-of-Concept Study. A Report on Behalf of the International Immuno-Oncology Biomarker Working Group

Cited by 11 publications

References 52 publications

Reinventing Nuclear Histo-score Utilizing Inherent Morphologic Cutoffs: Blue-brown Color H-score (BBC-HS)

Reinventing Nuclear Histo-score Utilizing Inherent Morphologic Cutoffs: Blue-brown Color H-score (BBC-HS)

Atezolizumab in the treatment of patients with breast cancer

Predictive Biomarkers of Response to Neoadjuvant Chemotherapy in Breast Cancer: Current and Future Perspectives for Precision Medicine

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