This multicentre study assessed SLFN11 protein expression (by immunohistochemistry H-score) across 361 lung neuroendocrine neoplasms — 127 typical carcinoids (TC), 35 atypical carcinoids (AC), 152 LCNEC, and 47 SCLC — exploring correlations with molecular markers (Ki67, ASCL1, cMYC, pRb, DLL3, etc.) and clinical outcomes including OS.
SLFN11 expression followed a clear histologic gradient (median H-score: TC=0, AC=0, LCNEC=2.49, SCLC=35; p<0.001) and correlated with Ki67 (R²=0.187). In SCLC, high SLFN11 (≥ median) was associated with improved OS (13.9 vs 6.8 months; HR=0.48, 95% CI 0.26–0.90, p=0.020). SLFN11 was linked to ASCL1-high tumors across all subtypes but was not prognostic in TC/AC or LCNEC.
- SCLC cohort was small (n=47), limiting statistical power for survival analysis. - Retrospective multicentre design with potential selection bias and IHC variability across centres. - Therapeutic implications (e.g., response to DNA-damaging agents) were not directly tested; clinical correlation is inferential.
SLFN11 expression is highest in SCLC and lowest in carcinoids, suggesting its predictive value for DNA-damaging therapies is most relevant in SCLC, particularly in ASCL1-high tumors. Its role in LCNEC and carcinoids remains unclear and should not yet guide treatment decisions.
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