Interobserver Variation of PD-L1 SP142 Immunohistochemistry Interpretation in Breast Carcinoma: A Study of 79 Cases Using Whole Slide Imaging

Abstract

Context.— The Ventana programmed death ligand-1 (PD-L1) SP142 immunohistochemical assay (IHC) is approved by the US Food and Drug Administration as the companion diagnostic assay to identify patients with locally advanced or metastatic triple-negative breast cancer for immunotherapy with atezolizumab, a monoclonal antibody targeting PD-L1. Objective.— To determine interobserver variability in PD-L1 SP142 IHC interpretation in invasive breast carcinoma. Design.— The pathology database was interrogated for all patients diagnosed with primary invasive, locally recurrent, or metastatic breast carcinoma on which PD-L1 SP142 IHC was performed from November 2018 to June 2019 at our institution. A subset of cases was selected using a computerized random-number generator. PD-L1 IHC was evaluated in stromal tumor-infiltrating immune cells using the IMpassion130 trial criteria, with positive cases defined as immunoreactivity in immune cells 1% or more of the tumor area. IHC was interpreted on whole slide images by staff pathologists with breast pathology expertise. Interobserver variability was calculated using unweighted κ. Results.— A total of 79 cases were assessed by 8 pathologists. Interobserver agreement was substantial (κ = 0.727). There was complete agreement among all 8 pathologists in 62% (49 of 79) of cases, 7 pathologists or more in 84% (66 of 79) of cases and 6 pathologists or more in 92% (73 of 79) of cases. In 4% (3 of 79) of cases, all of which were small biopsies, pathologists' interpretations were evenly split between scores of positive and negative. Conclusions.— The findings show substantial agreement in PD-L1 SP142 IHC assessment of breast carcinoma cases among 8 pathologists at a single institution. Further study is warranted to define the basis for discrepant results.

Digital validation of breast biomarkers (ER, PR, AR, and HER2) in cytology specimens using three different scanners

“…Others have evaluated digitally reporting prognostic immunohistochemical factors such as PDL-1 and HER2 in breast cancers and showed similar concordance results. Two studies of digital HER2 and PDL-1 reporting showed substantially equivalent kappa co-efficient (0.72) and percent agreement ranging from 61% −92 in 180 and 79 cases; respectively 36 , 41 , others have confirmed these findings and concluded there is non-inferiority for interpreting breast markers IHC by either glass slides or digital images 37 .Not surprisingly, 90–97% concordance of glass/digital pairs for all pathologists seen in this study are comparable those published in the literature.…”

“…Studies have attempted to use WSI to validate primary diagnosis in multiple surgical pathology specialty applications 12 including prostate 33 , pediatric 6 , dermatopathology 14 , gastrointestinal 16 , 19 , and gynecological pathology specimens 34 . Krenacs et al was among the first to address the potential use of digital imaging in breast cancer 18 .This was further followed by using WSI in primary breast cancer diagnosis 17 , 28 and in reporting prognostic factors such as the Nottingham histology grading 17 , 35 , PDL-1 36 and HER2 immunohistochemistry stains 37 , 38 in histology specimens.…”

Interobserver variability in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative invasive breast carcinoma influences the association with pathological complete response: the IVITA study

“…Other immune checkpoint inhibitors such as durvalumab are currently being evaluated in a clinical trial setting. Despite the poor reproducibility of PD-L1 assessment in a prospective multi-institutional assessment [ 47 ], the interobserver variation seems more limited within a single institution [ 48 ]. PD-L1 expression in sTILs might be useful to identify patients at high risk for poor therapeutic response.…”

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

“…Considering that the PD-L1/SP142 status of breast cancers depends on the number of tumor-infiltrating immune cells, a combined TILs-PD-L1 assessment may be a logical path forward to pursue [ 19 ]. Previous studies of variable size have reported the interobserver reproducibility of PD-L1/SP142 assessment in breast cancer samples, and their results varied from poor to very good [ 22 , 23 ]. Interobserver variability seems more limited within a single institution [ 23 ].…”

“…Previous studies of variable size have reported the interobserver reproducibility of PD-L1/SP142 assessment in breast cancer samples, and their results varied from poor to very good [ 22 , 23 ]. Interobserver variability seems more limited within a single institution [ 23 ]. These discrepant results could be explained by the heterogeneous set-up of these studies, with respect to the training and the number of the participating pathologists, and the number of TNBC samples evaluated.…”