Dataset Information

Molecular Characterization and Prognostication of Large Cell Neuroendocrine Carcinoma and Large Cell Carcinoma.

ABSTRACT:

Purpose

Large cell neuroendocrine carcinoma (LCNEC) and classic large cell carcinoma (LCC) are two distinct entities with different histological and biological characteristics. However, the mutational profiles and the clinical behavior of the two subtypes of lung cancer remain to be explored.

Patients and methods

Pathological diagnoses of all screened patients were finally confirmed by three or four experienced pathologists. Patients with uncertain pathological diagnoses were excluded. Finally, we genetically profiled ten patients with LCNEC and seven with LCC. ALL patients were subjected to next-generation sequencing (NGS) test, which included nine patients sequenced with a 139-gene panel and eight patients with a 425-gene panel. Including only intersected mutations from these two panels, survival analysis was further conducted.

Results

Both LCNEC and LCC showed high prevalence in male patients, with no clear association with smoking history. Potential targetable mutations in KRAS and RET were detected in the study cohort. However, LCNEC and LCC showed distinct mutational profiles with an enrichment of RB1/TP53 co-mutations in a subset of LCNEC patients. SMARCA4 and KEAP1 mutations were exclusively found in LCC patients, and RICTOR, BRAF, ROS1 and TET2 mutations were only detected in LCNEC. LCC patients in the cohort had shorter survival compared to LCNEC patients (p=0.006). Survival analysis revealed an association between SMARCA4 mutations and poor outcome in the study cohort and in the LCC subset. Mutations in BRAF were associated with a trend of increased survival in the study cohort, as well as in the LCNEC subset. Finally, TET2 mutations were associated with poor outcome in the LCNEC cohort.

Conclusion

LCC and LCNEC were both heterogeneous diseases with limited treatment options. Our study identified potential targetable mutations and prognostic biomarkers that might provide more therapeutic options and improve individualized patient care.

SUBMITTER: Chen Y

PROVIDER: S-EPMC8796852 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: In 2015, large cell neuroendocrine carcinoma (LCNEC) was removed from the large cell carcinoma group and classified with small cell lung carcinoma (SCLC) constituting two members of the high-grade neuroendocrine tumors (NETs) of the lung. However, the difference between high-grade LCNEC and SCLC in terms of clinicopathological characteristics and prognosis has not been fully understood owing to the rarity of LCNEC. Patients and methods: Patients with high-grade LCNEC and SCLC at initial diagnosis between 2001 and 2014 were identified using the Surveillance, Epidemiology, and End Results (SEER) program database. Clinicopathological characteristics between high-grade LCNEC and SCLC were compared using the Pearson's chi-squared test or Fisher's exact test. Differences in overall survival (OS) and cancer-specific survival (CSS) were compared using the log-rank test, Cox models and propensity score matching (PSM) analysis. Results: A total of 1223 patients with high-grade LCNEC and 18182 patients with high-grade SCLC were enrolled. To the best of our knowledge, this study involved the largest number of high-grade LCNEC patients to date, with respect to a comparison between high-grade LCNEC and high-grade SCLC patients. There were significant differences in age, sex, race, laterality, SEER stage, nodal status, surgery, radiation and chemotherapy, but not marital status, between high-grade LCNEC and SCLC patients. High-grade LCNEC patients had a better OS and CSS than high-grade SCLC patients. Subgroup analysis also confirmed the better prognosis of the high-grade LCNEC patients in the regional stage, distant stage and surgery subgroups. However, no significant difference in prognosis was observed between the two non-surgery subgroups, which was confirmed using PSM analysis. Furthermore, high-grade LCNEC patients showed different metastatic patterns to high-grade SCLC patients. Conclusion: These results suggested that high-grade LCNEC and high-grade SCLC were different histological types, and that a detailed classification for high-grade NETs of the lung was needed.