Genomic and immunophenotypic landscape of early-stage pulmonary carcinoid tumors.

Abstract

8030 Background: Pulmonary carcinoids (PCs), which encompass atypical carcinoids (ACs) and typical carcinoids (TCs), represent a rare category of lung cancer characterized by low to moderate malignancy. However, there is a limited understanding of the genomic and immune characteristics associated with PCs on a global scale. Methods: This study included a cohort of 126 surgically resectable Chinese PC patients, comprising 44 ACs and 82 TCs. Next-generation sequencing utilizing a 578-gene panel was conducted on 90 of PC patients, followed by the calculation of tumor mutation burden (TMB). Additionally, immunohistochemical staining for PD-L1 (n=108) and CD8 (n=94) was carried out to investigate the characteristics of the tumor microenvironment in PCs. Results: The most frequently altered genes in early-stage PCs were identified as EGFR (n=16, 18%), KMT2C (n=11, 12%), LRP1B (n=10, 11%), MEN1 (n=10, 11%), and NOTCH2 (n=9, 10%). Dysregulation of the RTK/RAS, NOTCH, and PI3K pathways was commonly observed in these PCs. Notably, genetic alterations in TP53, ARID1A, and CUL3 were more prevalent in ACs compared to TCs. However, TMB, PD-L1 expression, and CD8+ T cell infiltration were found to be low in early-stage PCs, with no significant differences observed between ACs and TCs. We identified age, gender, TNM stage, tumor type, smoking status, TMB, and LRP1B mutation, as indicators of poor prognosis, and further established a molecular classification that categorizes early-stage PCs into three distinct subtypes, each associated with varying clinical outcomes. Conclusions: We depicted the genetic and immune landscape of early-stage PCs and subsequently proposed a molecular classification based on the status of LRP1B mutation and smoking history. Our research offers novel insights into the biological mechanisms of PCs which contributes to the individualized treatment for Chinese PC patients.