The genomic and immunologic profiles of pure pulmonary sarcomatoid carcinoma in Chinese patients.
PURPOSE
The distribution of genetic mutations differs between pure pulmonary sarcomatoid carcinoma (PSC) and biphasic PSC; however, most of the enrolled cases in previous studies are biphasic PSC. The current study aimed to investigate the genomic and immunologic profiles of pure PSC in the Chinese population.


MATERIALS AND METHODS
Next-generation sequencing analysis of a panel of 1021 genes was performed on surgical specimens of 58 pure PSCs. The tumor mutational burden (TMB) was calculated from 0.69 megabases (Mbs) of sequenced DNA. PD-L1 expression was evaluated by immunohistochemistry. Microsatellite instability (MSI) was evaluated by fluorescence-labeled microsatellite marker polymerase chain reaction followed by capillary electrophoresis fragment size analysis.


RESULTS
The top mutational genes of pure PSC were TP53 (74 %, 43/58), KRAS (24 %, 14/58), SMARCA4 (14 %, 8/58), MET (12 %, 7/58), EGFR (10 %, 6/58), MLL4 (10 %, 6/58), NF1 (10 %, 6/58), NOTCH4 (10 %, 6/58), and TERT (10 %, 6/58). The median TMB was 8.6 mutations/Mb; 37.9 % of cases (22/58) had a TMB > 10 mutations/Mb and 12.1 % of cases (7/58) had a TMB > 20 mutations/Mb. The median TMB was higher in TP53-mutant tumors than in wild-type tumors (10.1 versus 7.2 mutations/Mb, p = 0.019). Thirty-five patients had microsatellite-stable pure PSC, and four patients carried MSI-H tumors. The MSI status was independent of MET exon 14 status. Twenty-six patients (45 %) had PD-L1-positive tumors (≥1%) and 14 (24 %) had high PD-L1 expression (≥50 %).


CONCLUSION
In our cohort, 45 % of patients with pure PSC harbored at least one actionable alteration. More importantly, more than 60 % of patients (65.5 %, 38/58) had either MSI-H, PD-L1-positive, or high-TMB tumors, and these might derive survival benefits from immune checkpoint inhibitors.
['Zhou|Fei|F|', 'Huang|Yan|Y|', 'Cai|Weijing|W|', 'Li|Jin|J|', 'Su|Chunxia|C|', 'Ren|Shengxiang|S|', 'Wu|Chunyan|C|', 'Zhou|Caicun|C|']
D060890:B7-H1 Antigen D002277:Carcinoma D002681:China D004265:DNA Helicases D023281:Genomics D006801:Humans D008175:Lung Neoplasms D053842:Microsatellite Instability D009154:Mutation D009687:Nuclear Proteins D014157:Transcription Factors
Pulmonary sarcomatoid carcinoma Tumor mutational burden PD-L1 expression Microsatellite instability Molecular alteration