Dataset Information

PD-L1 Expression in Metaplastic Breast Carcinoma Using the PD-L1 SP142 Assay and Concordance Among PD-L1 Immunohistochemical Assays.

ABSTRACT: Immunotherapy for the treatment of programmed death-ligand 1 (PD-L1) positive locally advanced or metastatic triple negative breast cancer may benefit patients with metaplastic breast cancer (MpBC). Previous study of PD-L1 in MpBC scored tumor cells (TCs), different from Food and Drug Administration-approved scoring methods. We sought to define PD-L1 expression in MpBCs and to evaluate concordance of 3 PD-L1 assays. Primary, treatment naive MpBC treated at our Center from 1998 to 2019 were identified. PD-L1 expression was assessed using SP142, E1L3n, and 73-10. We evaluated PD-L1 expression on tumor infiltrating immune cells (IC) and also in TCs. For each assay, we scored PD-L1 expression using ≥1% IC expression according to the IMpassion130 trial criteria and using combined positive score (CPS) ≥10 according to the KEYNOTE-355 trial cutoff. A total of 42 MpBCs were identified. Most MpBC had PD-L1 positivity in ≥1% IC with all 3 assays (95%, 95%, 86%) in contrast to a maximum 71% with a CPS ≥10. PD-L1 IC expression was comparable between the SP142 and 73-10 assays and was lowest with E1L3n. PD-L1 TC expression was lowest using SP142. The overall concordance for IC scoring was 88% while 62% had concordant CPS. For each assay, the results of the 2 scoring algorithms were not interchangeable. The SP142 assay showed distinct expression patterns between IC (granular, dot-like) and TC (membranous) while 73-10 and E1L3n showed membranous and/or cytoplasmic expression in both IC and TC. Most MpBC in our cohort were positive for PD-L1 indicating eligibility for anti-PD-L1/programmed death-1 immunotherapy.

SUBMITTER: Grabenstetter A

PROVIDER: S-EPMC9437740 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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PD-L1 Expression in Metaplastic Breast Carcinoma Using the PD-L1 SP142 Assay and Concordance Among PD-L1 Immunohistochemical Assays.

Grabenstetter Anne A Jungbluth Achim A AA Frosina Denise D Hoda Raza R Dos Anjos Carlos H CH Patil Sujata S Sevilimedu Varadan V Weigelt Britta B Reis-Filho Jorge S JS Zhang Hong H Traina Tiffany T Robson Mark E ME Brogi Edi E Wen Hannah Y HY

The American journal of surgical pathology 20210901 9

Immunotherapy for the treatment of programmed death-ligand 1 (PD-L1) positive locally advanced or metastatic triple negative breast cancer may benefit patients with metaplastic breast cancer (MpBC). Previous study of PD-L1 in MpBC scored tumor cells (TCs), different from Food and Drug Administration-approved scoring methods. We sought to define PD-L1 expression in MpBCs and to evaluate concordance of 3 PD-L1 assays. Primary, treatment naive MpBC treated at our Center from 1998 to 2019 were ident ...[more]

PMID: 34115674

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Project description:PurposeThe discernible PD-L1 staining of tumor-infiltrating lymphocytes occupying ≥ 1% of the tumor area is considered SP142 PD-L1 positive for atezolizumab, and the PD-L1 status of multiple samples within a single patient could be discrepant. In this study, we evaluated the PD-L1 status by using the SP142 clone in serially collected matched samples from the same individuals with early or metastatic triple-negative breast cancer (TNBC).Methodthe SP142 PD-L1 assay was performed using biopsies and surgical specimens from 77 patients with early TNBC. Among these patients, 47 underwent upfront surgery, and 30 underwent neoadjuvant chemotherapy (NAC) between biopsy and surgery. PD-L1 assays were performed at least twice in 8/12 (66.7%) patients with metastatic TNBC treated with atezolizumab and nab-paclitaxel.ResultsOf the 47 patients who underwent upfront surgery, 15/47 (31.9%) had PD-L1+ on biopsied samples. PD-L1+ rates in the biopsy and surgical specimens increased to 66.0% (33 of 47) after subsequent surgery. Similarly, in the 30 patients with residual invasive cancer who underwent neoadjuvant chemotherapy, the PD-L1+ rate increased from 46.6% at baseline to 74.2% after surgery. In the 77 patients with early TNBC, multiple PD-L1 testing in the biopsies and surgical specimens significantly increased the number of patients with PD-L1+ compared with the number of patients with PD-L1+ assessed with initial biopsy samples alone (68.8% vs. 37.6%; p = 0.00002). Among the metastatic TNBC patients, those with constant PD-L1+ over 1% positivity in multiple samples showed a response which was longer than 12 months.ConclusionsOur findings reveal the heterogeneous SP142 PD-L1 expression in TNBC and suggest that PD-L1 evaluation in baseline biopsy might be insufficient to represent the PD-L1 status of whole tumors. In TNBC, vigorous PD-L1 examination using multiple available tumor samples could identify more patients eligible for immune checkpoint blockade.

Project description:Thymoma is a relatively rare malignancy, which is categorized as thymic epithelial tumor but known as the most common pathology that is developed in the anterior mediastinum. Complete resection is recommended for localized tumors and usually favorable prognosis can be obtained. However, poor survival period has been reported in unresectable cases exhibiting extensive invasion or distant metastasis, as effective chemotherapeutic regimens are restrained. We previously assessed expression of programmed death ligand 1 (PD-L1) and programmed death 1 (PD-1) and discussed their prospective application in the immunotherapy of thymic epithelial tumors. After our publication, additional studies using reliable PD-L1 antibodies, which are currently administered to predict efficacy of PD-1/PD-L1 blockade therapy were performed and further characterized PD-L1 in thymoma. Herein, recent knowledge in relation to the significance of PD-L1 expression in thymoma is reviewed based on recent findings using qualified PD-L1 clones. Most studies coherently found high expression of PD-L1 on the cell membrane and cytoplasm of tumor epithelial cells in accordance with previous reports, which is a predictive marker for effectiveness of anti-PD-1/PD-L1 drugs, even when approved PD-L1 antibodies were employed. On the other hand, PD-L1 expression on tumor infiltrating immune cells remains to be sufficiently determined. High PD-L1 expression can be expected in cases with high grade histological subtypes, such as type B2/B3 thymomas, or those with advanced stages III or IV of the disease. Interestingly, the level of PD-L1 expression was found to be upregulated after chemotherapy compared with that before, which could be explained by immunogenic cell death. The prognostic impact of PD-L1 expression in thymoma might be found only when thymic carcinoma patients were excluded. Furthermore, it also could be identified when we analyzed thymomas completely resected, distinct from biopsy and incompletely resected cases.

Dataset Information

PD-L1 Expression in Metaplastic Breast Carcinoma Using the PD-L1 SP142 Assay and Concordance Among PD-L1 Immunohistochemical Assays.

Publications

PD-L1 Expression in Metaplastic Breast Carcinoma Using the PD-L1 SP142 Assay and Concordance Among PD-L1 Immunohistochemical Assays.

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