Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Pleomorphic Lobular Breast Carcinoma

Version 1 : Received: 27 April 2023 / Approved: 28 April 2023 / Online: 28 April 2023 (03:22:03 CEST)

A peer-reviewed article of this Preprint also exists.

Göker, M.; Deblaere, S.; Denys, H.; Vergauwen, G.; Naert, E.; Veldeman, L.; Monten, C.; Van den Broecke, R.; Van Dorpe, J.; Braems, G.; Van de Vijver, K. Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Pleomorphic Lobular Breast Carcinoma. Cancers 2023, 15, 2894. Göker, M.; Deblaere, S.; Denys, H.; Vergauwen, G.; Naert, E.; Veldeman, L.; Monten, C.; Van den Broecke, R.; Van Dorpe, J.; Braems, G.; Van de Vijver, K. Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Pleomorphic Lobular Breast Carcinoma. Cancers 2023, 15, 2894.

Abstract

Background: The prognostic and predictive role of stromal tumor-infiltrating lymphocytes (sTILs) is undetermined in pleomorphic invasive lobular cancer (pILC). The same applies for the expression of PD-1/PD-L1 in this rare breast cancer subtype. Here, we aimed to investigate the expression of sTILs, and analyze the PD-L1 expression levels in pILC. Methods: Archival tissues from sixty-six patients with pILC were collected. The sTIL density was scored as a percentage of tumor area, using the following cut-offs: 0%; <5%; 5-9%; and 10-50%. PD-L1 expression was analyzed using IHC on formalin-fixed, paraffin-embedded tissue sections, using the SP142 and 22C3 antibodies. Results: 82% of the sixty-six patients were hormone receptor-positive; 8% of cases were triple negative (TN), while 10% showed human epidermal growth factor receptor 2 (HER2) amplification. sTILs were present in 64% (1%) of the study population. Using the SP142 antibody, 36% of tumors demonstrated a positive PD-L1 score of 1%, and 28% had a positive PD-L1 score of 1 using the 22C3 antibody. There was no correlation of sTILs or PD-L1 expression with tumor size, tumor grade, nodal status, expression of estrogen receptor (ER) or amplification of HER2. Our data did not show any difference in survival between the three molecular subtypes of pILC with respect to sTILs and PD-L1 expression. Conclusion: This study shows that pILCs show some degree of sTILs and PD-L1 expression, however this was not associated with survival benefit. Additional large trials are needed to understand the immune infiltration in lobular cancer, even more in the pleomorphic subtype.

Keywords

Invasive lobular cancer; pleomorphic invasive lobular cancer; tumor-infiltrating lymphocytes; programmed cell death 1; programmed cell death ligand 1; 22C3 assay; SP142 assay; survival

Subject

Biology and Life Sciences, Immunology and Microbiology

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