2022 World Conference on Lung Cancer (ePosters)-EP11.01-013. Genomic Landscape of Pulmonary Sarcomatoid Carcinoma

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Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subtype of non-small cell lung cancer (NSCLC) with limited treatment options. In this study, researchers aimed to understand the genomic characteristics that contribute to the morphologic heterogeneity and progression of PSC. Thirty-one patients with surgically resected PSC tumors were included in the analysis.<br /><br />The study found that the most frequently altered gene in both primary and metastatic PSC samples was TP53, a known driver mutation in NSCLC. Other common mutations included EGFR, KRAS, MET, and KEAP1. MDM2 amplification was also observed in some cases. MET mutations were confirmed to be MET exon 14 skipping mutations.<br /><br />Phylogenetic analysis revealed that primary carcinomatous and sarcomatous components of the tumors had more genetic similarities than metastatic tumors. The study also identified mutational signatures associated with smoking and defective DNA mismatch repair. Metastatic tumors showed a reduced presence of the APOBEC mutational signature compared to primary tumors.<br /><br />Clinicopathologic characteristics of PSC patients included middle-aged men with a smoking history. Strong PD-L1 expression was observed in 61% of cases. The presence of more frequent MET and KEAP1 mutations, as well as strong PD-L1 expression, distinguished PSC from other NSCLC subtypes.<br /><br />Comparison with other NSCLC subtypes revealed that PSC had higher frequencies of MET and KEAP1 mutations regardless of ethnicity. These findings suggest that the genetic landscape of PSC differs from adenocarcinoma and squamous cell carcinoma.<br /><br />Based on these results, the study suggests that next-generation sequencing and PD-L1 expression analysis may be important for determining the appropriate treatment strategy for PSC patients. The genomic complexity and heterogeneity of PSC tumors likely contribute to its aggressive behavior and treatment challenges.

Asset Subtitle

Hyun Jung Kwon

Meta Tag

Speaker Hyun Jung Kwon

Topic Pathology - Genomics & Analytics

Keywords

Pulmonary sarcomatoid carcinoma

non-small cell lung cancer

genomic characteristics

TP53 mutation

EGFR mutation

KRAS mutation

MET mutation

KEAP1 mutation

PD-L1 expression

treatment strategy