<scp>TROP2</scp> immunoreactivity in pulmonary large cell neuroendocrine carcinoma

INTRODUCTION: TROP2 antibody-drug conjugates have shown promising anti-tumour activity, but neither the activity of these agents nor TROP2 expression has been well studied in pulmonary large cell neuroendocrine carcinoma (LCNEC), a rare and aggressive cancer type. We aimed to (i) determine the prevalence of TROP2 immunoreactivity in LCNEC; (ii) assess whether TROP2 immunoreactivity in LCNEC is related to RB1 loss on IHC or to the presence of NSCLC or SCLC components and (iii) determine whether TROP2 immunoreactivity in LCNEC has prognostic significance. METHODS: TROP2 immunohistochemistry was performed on 58 pure LCNECs and 25 areas of LCNEC that were combined with other carcinomas, in tissue microarray format. TROP2 was scored for the percent of tumour cells staining, and with evaluation of cytoplasmic versus membranous staining, approximating a previously published predictive scoring method. RESULTS: TROP2 staining in ≥1% and ≥50% of LCNEC cells was present in 60% and 26% of pure LCNEC tumours, respectively. Cytoplasmic-type staining, previously implicated in greater antibody-drug conjugate response, was present in 48% of pure LCNEC cases. Positive TROP2 staining was less frequent in pure LCNEC than in the LCNEC component of tumours that also contained a NSCLC component (≥1%: P = 0.0087; ≥50%: P = 0.011), and ≥50% TROP2 staining in pure LCNEC was associated with retained RB1 staining on immunohistochemistry (P = 0.032). TROP2 staining was not associated with recurrence-free survival or disease-specific survival outcomes. CONCLUSION: Frequently positive TROP2 IHC suggests that TROP2 antibody-drug conjugates may be potential treatments for LCNEC.