Comparison of PD-L1 (22C3) Expression in Paired Primary and Metastatic Breast Carcinoma

Xiao Huang; Sarah A Anderson; Gene P Siegal; Shi Wei; Shanrun Liu; Jingyun Yang; Puentes Roisin; J Taylor Pickens; Lei Huo; Aysegul A Sahin; Carlos Prieto Granada; Shuojun Chen

doi:10.1016/j.clbc.2024.02.010

Comparison of PD-L1 (22C3) Expression in Paired Primary and Metastatic Breast Carcinoma

Clin Breast Cancer. 2024 Feb 16:S1526-8209(24)00046-6. doi: 10.1016/j.clbc.2024.02.010. Online ahead of print.

Authors

Affiliations

¹ Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL. Electronic address: xiaohuang@uabmc.edu.
² Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL.
³ Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS.
⁴ Department of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL.
⁵ Department of Neurological Sciences, RUSH University, Chicago, IL.
⁶ NeoGenomics laboratories, Inc. Aliso Viejo, CA.
⁷ Department of Pathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
⁸ Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN.

PMID: 38492995
DOI: 10.1016/j.clbc.2024.02.010

Abstract

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.

Keywords: Breast cancer; Fluorescence in situ hybridization; Next generation sequencing; PD-L1; Progression.