Evaluation of trophoblast cell surface antigen-2 (TROP2) protein expression in chemotherapy-resistant and metastatic breast carcinomas.

Autor: Van Bockstal MR; Department of Pathology, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, Brussels 1200, Belgium; Pôle de Morphologie (MORF), Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Avenue Hippocrate 10, Brussels 1200, Belgium. Electronic address: Mieke.VanBockstal@saintluc.uclouvain.be., Depelsemaeker MC; Department of Pathology, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, Brussels 1200, Belgium., Daoud L; Department of Pathology, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, Brussels 1200, Belgium., Fontanges Q; Department of Pathology, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, Brussels 1200, Belgium., Francois A; Department of Pathology, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, Brussels 1200, Belgium., Guiot Y; Department of Pathology, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, Brussels 1200, Belgium., Dekairelle AF; Department of Molecular Biology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Avenue Hippocrate 10, Brussels 1200, Belgium., Dubois D; Department of Pathology, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, Brussels 1200, Belgium., Van Marcke C; Pôle d'imagerie moléculaire, radiothérapie et oncologie (MIRO), Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Avenue Hippocrate 10, Brussels 1200, Belgium; Department of Medical Oncology, King Albert II Cancer Institute, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, Brussels 1200, Belgium., Longton E; Breast Clinic, King Albert II Cancer Institute, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, Brussels 1200, Belgium; Department of Radiation Oncology, King Albert II Cancer Institute, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, Brussels 1200, Belgium., Duhoux FP; Pôle d'imagerie moléculaire, radiothérapie et oncologie (MIRO), Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Avenue Hippocrate 10, Brussels 1200, Belgium; Department of Medical Oncology, King Albert II Cancer Institute, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, Brussels 1200, Belgium., Vernaeve H; Breast Clinic, Clinique Saint-Jean, Boulevard du Jardin Botanique 32, Brussels 1000, Belgium., Berlière M; Breast Clinic, King Albert II Cancer Institute, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, Brussels 1200, Belgium; Pôle de Gynécologie (GYNE), Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Avenue Hippocrate 10, Brussels 1200, Belgium., Floris G; Department of Oncology, KU Leuven, Herestraat 49, Box 7003-06, Leuven 3000, Belgium; Department of Imaging & Pathology, University Hospitals Leuven, Herestraat 49, Leuven 3000, Belgium., Galant C; Department of Pathology, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, Brussels 1200, Belgium; Pôle de Morphologie (MORF), Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Avenue Hippocrate 10, Brussels 1200, Belgium.
Jazyk: angličtina
Zdroj: Pathology, research and practice [Pathol Res Pract] 2024 Dec; Vol. 264, pp. 155724. Date of Electronic Publication: 2024 Nov 16.
DOI: 10.1016/j.prp.2024.155724
Abstrakt: Trophoblast cell-surface antigen 2 (TROP2), a transmembrane receptor expressed in many carcinomas, is a target for novel antibody-drug conjugates such as sacituzumab govitecan. TROP2-targeted therapy is used for unresectable locally advanced or metastatic triple-negative and hormone receptor-positive, HER2-negative breast cancers. The role of TROP2 as a predictive marker is yet unclear. Standardized interpretation criteria for TROP2 immunohistochemistry (IHC) are lacking. Here, we compared three antibody clones and two methods for semi-quantitative assessment, aiming to establish reproducible evaluation criteria. First, TROP2 IHC was performed on normal tissues and nine breast cancers, using the BSB-148, EPR20043 and SP293 clones. EPR20043 was selected for subsequent evaluation in 69 breast cancers without pathological complete response to neoadjuvant chemotherapy (NAC). Four pathologists applied the ASCO/CAP guidelines for HER2 IHC testing (designated as the 'membrane score') and the H-score. All H-scores were categorized as low (0-100), intermediate (101-200) and high (201-300). Although the membrane scores strongly correlated with the categorized H-scores, the latter showed higher interobserver variability. Next, TROP2 IHC was performed on 94 breast cancer metastases and evaluated by six pathologists, confirming the strong correlation between the membrane scores and H-scores. In metastases, the interobserver variability was similar for both methods. Our observations support the application of the HER2 ASCO/CAP guidelines for semi-quantitative evaluation of membranous TROP2 protein expression, as this method strongly correlates with the H-score and is less prone to interobserver variability in post-NAC breast resections. Future studies should investigate the association between the TROP2 membrane score and response to TROP2-targeted therapy.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mieke R. Van Bockstal reports financial support was provided by Saint-Luc Foundation. Mieke R. Van Bockstal reports financial support was provided by Foundation Against Cancer. Christine Galant reports financial support was provided by Saint-Luc Foundation. Francois Duhoux reports financial support was provided by Foundation Against Cancer. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier GmbH. All rights reserved.)
Databáze: MEDLINE
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