PMID- 38492995 OWN - NLM STAT- Publisher LR - 20240316 IS - 1938-0666 (Electronic) IS - 1526-8209 (Linking) DP - 2024 Feb 16 TI - Comparison of PD-L1 (22C3) Expression in Paired Primary and Metastatic Breast Carcinoma. LID - S1526-8209(24)00046-6 [pii] LID - 10.1016/j.clbc.2024.02.010 [doi] AB - INTRODUCTION: PD-L1 immunohistochemistry (IHC) is being used as a predictive marker of the benefit derived from immunotherapy in several cancer types, including breast cancer. However, the insight gleaned of the prognostic and predictive value of PD-L1 status and its correlation with molecular characteristics during breast cancer progression remains limited. METHODS: We performed an PD-L1 (22C3) assay in pre-treatment primary and metastatic tumor sections from 33 patients with breast carcinoma, matched for post neoadjuvant chemotherapy (p-NACT). PD-L1 expression was evaluated using 3 scoring methods: immune cell (IC) and tumor cell (TC) with a 1% as the cutoff value, and combined positive scores (CPS) with a 1 as the cutoff value. Twenty-two samples from 11 patients had successful fluorescence in situ hybridization (FISH)-based molecular data available for analysis. RESULTS: In the 33 pre-treatment primary tumors, PD-L1 IC, TC, and CPS showed positive correlation with stromal tumor infiltrate lymphocytes (sTIL), histological grade 3, and triple negative breast carcinoma (TNBC). In the matched metastatic tumors, only PD-L1 IC showed a positive correlation with sTIL. The primary tumors showed a higher PD-L1 expression than the matched metastatic tumors by IC and CPS. Negative to positive conversion by CPS was identified in the metastatic tumors from lung, pleura and liver. p-NACT tumors also showed a trend of lower PD-L1 expression compared to the pre-treatment tumors. Six patients had matched samples for molecular and PD-L1 comparison, and none of them showed consistent gene alterations or PD-L1 expression among the primary, p-NACT and metastatic tumors. CONCLUSION: Our study showed a decrease in PD-L1 expression and disconnected molecular features during breast cancer progression. Repeating PD-L1 IHC testing could be considered in some specific metastatic sites if primary tumors were negative. Further studies are needed to identify other predictive factors for immune checkpoint inhibitor (ICI) therapy in patients with breast carcinoma. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Huang, Xiao AU - Huang X AD - Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL. Electronic address: xiaohuang@uabmc.edu. FAU - Anderson, Sarah A AU - Anderson SA AD - Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL. FAU - Siegal, Gene P AU - Siegal GP AD - Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL. FAU - Wei, Shi AU - Wei S AD - Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS. FAU - Liu, Shanrun AU - Liu S AD - Department of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL. FAU - Yang, Jingyun AU - Yang J AD - Department of Neurological Sciences, RUSH University, Chicago, IL. FAU - Roisin, Puentes AU - Roisin P AD - NeoGenomics laboratories, Inc. Aliso Viejo, CA. FAU - Pickens, J Taylor AU - Pickens JT AD - Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL. FAU - Huo, Lei AU - Huo L AD - Department of Pathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Sahin, Aysegul A AU - Sahin AA AD - Department of Pathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Granada, Carlos Prieto AU - Granada CP AD - Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN. FAU - Chen, Shuojun AU - Chen S AD - Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL. LA - eng PT - Journal Article DEP - 20240216 PL - United States TA - Clin Breast Cancer JT - Clinical breast cancer JID - 100898731 SB - IM OTO - NOTNLM OT - Breast cancer OT - Fluorescence in situ hybridization OT - Next generation sequencing OT - PD-L1 OT - Progression COIS- Disclosure No authors have any conflicts of interest to disclose. EDAT- 2024/03/17 00:42 MHDA- 2024/03/17 00:42 CRDT- 2024/03/16 22:57 PHST- 2023/10/04 00:00 [received] PHST- 2024/01/18 00:00 [revised] PHST- 2024/02/12 00:00 [accepted] PHST- 2024/03/17 00:42 [medline] PHST- 2024/03/17 00:42 [pubmed] PHST- 2024/03/16 22:57 [entrez] AID - S1526-8209(24)00046-6 [pii] AID - 10.1016/j.clbc.2024.02.010 [doi] PST - aheadofprint SO - Clin Breast Cancer. 2024 Feb 16:S1526-8209(24)00046-6. doi: 10.1016/j.clbc.2024.02.010.