In this study, we investigated human epidermal growth factor receptor 2 (HER2) aberrations, including gene amplification and mutation, and protein expression in 123 small cell lung carcinomas (SCLC) and 128 extrapulmonary small cell neuroendocrine carcinomas (EP-SCNC) samples. Among the EP-SCNC cohort, HER2 mutations were found in 5.5% of samples (7/128); urinary bladder (4 cases), and one case each in samples from the colon, anal canal, and uterine cervix. In SCLCs, HER2 mutations were rare, detected in only 0.8% (1/119) of cases. We also identified eight EP-SCNCs and five SCLC cases with HER2 gene variants of uncertain significance (VUS). HER2 gene amplification was detected in 2.3% (3/128) of EP-SCNCs, but no amplification was found in SCLCs. The differences in HER2 mRNA expression were not statistically significant among tumor groups in the EP-SCNCs and SCLCs cohorts. RNA-seq analysis revealed high HER2 mRNA expression in seven EP-SCNCs and four SCLCs. An immunohistochemistry (IHC) analysis of 10 available tumors with high mRNA expression revealed HER2 protein positivity in 8 cases. The prognostic value of HER2 overexpression in EP-SCNC patients was not established in our study. Furthermore, EP-SCNC patients with high HER2 mRNA expression were generally younger, with a mean age of 60 years. These findings highlight the potential of HER2 as a therapeutic target in EP-SCNC, warranting further investigation into its clinical implications.

Department of Anaesthesia and Intensive Care 3rd Faculty of Medicine Charles University and University Hospital Kralovske Vinohrady Prague Czech Republic

Department of Oncological Pathology Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Pathology 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Department of Pathology 3rd Faculty of Medicine University Hospital Kralovske Vinohrady Charles University Prague Czech Republic

Department of Pathology and Molecular Medicine 3rd Faculty of Medicine Thomayer University Hospital Charles University Prague Czech Republic

Department of Respiratory Medicine 1st Faculty of Medicine Charles University and Thomayer University Hospital Prague Czech Republic

Šikl's Department of Pathology Faculty of Medicine and University Hospital in Pilsen Charles University Pilsen Czech Republic

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