Abstract 5452: Neuroendocrine negative RB1 WT SCLC and LCNEC

Abstract

Abstract Background: Based on genomics data generated in last few years about 15% of tumors diagnosed as large cell neuroendocrine carcinomas (LCNEC) are actually neuroendocrine negative. Interestingly, approximately similar percentage of small cell lung cancers (SCLC) are also neuroendocrine negative, historically known as SCLC variant and are enriched for RB1 WT tumors. Here we compare the morphological, genomic and other features of neuroendocrine negative RB1 WT SCLC and LCNEC. Methods: To comprehensively compare neuroendocrine RB1 WT SCLC and LCNEC, we examined morphological, genomic and other features of these rare lung cancer subtypes using publicly available data. From a genomics perspective, we payed special attention to key oncogenic genetic alterations and expression pattern of transcription factors known to play critical role in SCLC and LCNEC. Results/Conclusions: The expression pattern of transcription factors ASCL1, POU2F3, NEUROD1, YAP1 in LCNEC has number of similarities to expression pattern of these transcription factors in SCLC. Neuroendocrine negative/low RB1 WT SCLC and neuroendocrine negative/low, RB1 WT, KEAP1 WT, STK11 WT LCNEC have similar genomics and morphological characteristics and might be in fact the same entity. Based on differences in distribution of different lung cell types at different anatomical locations such as: peripheral, midzone or central, collecting information on lung tumor location along with genomic information and neuroendocrine markers staining could be important for better understanding of rare lung tumor subtypes. Clinical trial NCT04010357 is going to investigate efficacy of CDK4/6 inhibitor abemaciclib in RB1WT SCLC. Based on our observations patients with neuroendocrine negative/low RB1 WT, KEAP1 WT, STK11 WT LCNEC subtype might be also candidates for clinical trial-based treatment with CDK4/6 inhibitors. Citation Format: Dmitriy Sonkin, Anish Thomas, Beverly A. Teicher. Neuroendocrine negative RB1 WT SCLC and LCNEC [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5452.