Lung adenosquamous carcinomas (ASC) are morphologically mixed tumors that contain adenocarcinomas component (ACC) and squamous cell carcinomas component (SCCC). However, the genomic profile and immune microenvironment of each component remain unclear.
ACC and SCCC in ASC (n = 25) were validated by immunohistochemistry and obtained separately by means of laser capture microdissection. Gene panel and T cell receptor (TCR) repertoire sequencing were performed in both components. 578 adenocarcinomas (AC) and 82 squamous cell carcinomas (SCC) were also included for comparison with ASC.
Of 19 paired samples, two components in 94.7% cases had identical gene mutations. The most frequency mutated genes in trunk were EGFR (77.2%), TP53 (44.4%), MDM2 (16.7%), BRD4 (11.1%), CDK4 (11.1%), ERBB2 (11.1%), FAT1 (11.1%) and SMARCA4 (11.1%). Interestingly, the genomic profiles were different when comparing ACC with SCCC, ACC with AC and SCCC with SCC, respectively. MAP3K1 (15% vs. 4.6%) and NF1(15% vs. 4.6%) mutated more frequent in ACC (n = 20) when compared with SCCC (n = 22), while ARAF (13.6% vs. 0%), KEAP1 (13.6% vs. 0%), ALK (13.6% vs. 5%) and PIK3CA (13.6% vs. 5%) in SCCC when compared with ACC. KRAS (11.1%) and APC (7.1%) were observed in AC samples (n = 578), but not in ACC. CDKN2A (24.4%) was exclusive in SCC samples (n = 82) but not in SCCC. Moreover, mutation frequency of EGFR was much higher in SCCC compared with SCC (68.2% vs. 20.7%). The TCR repertoire of two components were markedly different from each other, 57.1% (12/21) paired samples exhibited extremely low level in Morisita-Horn overlap (range from 0 -0.194, mean: 0.09). In addition, TCR clonotype was found in a strong positive correlation with CA125 (p = 0.017, r = 0.70, n = 11) in ACC and with NSE (p = 0.006, r = 0.80, n = 10) in SCCC, respectively.
Our data support the hypothesis that ACC and SCCC in ASC come from the same origin. Diverse genomic profile were exhibited between ACC and SCCC, AC and ACC and SCC and SCCC, which indicated ASC was an unique pathological subtype. TCR repertoire is also distinct in two components in line with the results of genomic profile. Limited by a small number of samples, our study is still ongoing for validation these findings.
Clinical trial identification
Legal entity responsible for the study
Fujian Cancer Hospital.
Fujian Provincial health systemic youth backbone training projects [grant number 2015-ZQN-ZD-9].
All authors have declared no conflicts of interest.