HER2-low in gastro-oesophageal adenocarcinoma: a real-world pathological perspective

AimsIn the DESTINY-Gastric01 trial, a novel HER2-targeted antibody-drug conjugate trastuzumab deruxtecan proved to be effective in HER2-low gastro-oesophageal adenocarcinomas. The aim of our study is to investigate the clinicopathological and molecular features of HER2-low gastric/gastro-oesophageal...

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Veröffentlicht in:Journal of clinical pathology 2023-12, Vol.76 (12), p.815-821
Hauptverfasser: Angerilli, Valentina, Parente, Paola, Campora, Michela, Ugolini, Clara, Battista, Serena, Cassoni, Paola, Gambella, Alessandro, Cavallin, Francesco, De Lisi, Giuseppe, Vanoli, Alessandro, Grillo, Federica, Mastracci, Luca, Fassan, Matteo
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Sprache:eng
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Zusammenfassung:AimsIn the DESTINY-Gastric01 trial, a novel HER2-targeted antibody-drug conjugate trastuzumab deruxtecan proved to be effective in HER2-low gastro-oesophageal adenocarcinomas. The aim of our study is to investigate the clinicopathological and molecular features of HER2-low gastric/gastro-oesophageal junction cancers in the real-world setting of a large multi-Institutional series.MethodsWe retrospectively evaluated 1210 formalin-fixed paraffin-embedded samples of gastro-oesophageal adenocarcinomas which were analysed by immunohistochemistry for HER2 protein expression in 8 Italian surgical pathology units from January 2018 to June 2022. We assessed the prevalence of HER2-low (ie, HER2 1+ and HER2 2+ without amplification) and its correlation with clinical and histopathological features, other biomarkers’ status, including mismatch repair/microsatellite instability status, Epstein-Barr encoding region (EBER) and PD-L1 Combined Positive Score.ResultsHER2 status could be assessed in 1189/1210 cases, including 710 HER2 0 cases, 217 HER2 1+, 120 not amplified HER2 2+, 41 amplified HER2 2+ and 101 HER2 3+. The estimated prevalence of HER2-low was 28.3% (95% CI 25.8% to 31.0%) overall, and was higher in biopsy specimens (34.9%, 95% CI 31.2% to 38.8%) compared with surgical resection specimens (21.0%, 95% CI 17.7% to 24.6%) (p
ISSN:0021-9746
1472-4146
DOI:10.1136/jcp-2023-208767