Abstract
BackgroundLung cancer is a public health problem, and squamous cell carcinoma (SCC) is the second most prevalent subtype of this neoplasm. Compared to other subtypes, including adenocarcinoma, SCC is less well understood in terms of molecular pathogenesis, limiting therapeutic options among targeted agents approved for other disease subgroups. In this study, we sought to characterize the SCC genomic profile using a validated Next Generation Sequencing (NGS) platform.MethodsThe comprehensive NGS assay (TruSight Tumor 170) was used in order to target the full coding regions of 170 cancer-related genes on SCC samples. PD-L1 expression in tumor cells (TCs) was assessed using clone 22C3 (Dako). Clinical outcomes were correlated with molecular profile, including progression free survival (PFS), overall response rate (ORR), and overall survival (OS).ResultsA total of 26 samples were included, median age was 67 years (r, 33–83) and 53.8% were men. Tobacco consumption was identified in all subjects (mean 34-year package). For first-line treatment 80.8% of patients received cisplatin or carboplatin plus gemcitabine. In terms of molecular profile, we identified a high prevalence of inactivating mutations in TP53 (61.5%), PIK3CA (34.6%), MLL2 (34.6%), KEAP1 (38.4%), and NOTCH1 (26.9%). PD-L1 expression ranged from negative, 1, 2–49, and ≥50% in 23.1, 38.5, 26.9, and 11.5%, respectively. Interestingly, the genetic alterations did not have an effect in PFS, OS or ORR in this study. However, PDL1 expression was higher among those who had mutations in TP53 (p = 0.037) and greater expression of PDL1 was related to PIK3CA alterations (p = 0.05).ConclusionsThe genomic profile of SCC encompasses important genes including TP53, PIK3CA and KEAP1. TP53 mutations could be associated with PDL1 expression, generating hypothesis regarding specific treatment options.
Highlights
The incidence of squamous cell carcinoma of the lung (SCC) has steadily fallen while the incidence of lung adenocarcinoma (LUAD) has risen over the last few decades
The median cigarette exposure was 34.4 packs-year. 21 patients presented with advanced disease (AJCC stage IV) and received cisplatin or carboplatin plus gemcitabine as first line therapy
The Next Generation Sequencing (NGS)-tested specimens included 17 FFPE sections taken from the primary (65.4%), followed by visceral and lymph node metastases in 6 cases (23%)
Summary
The incidence of squamous cell carcinoma of the lung (SCC) has steadily fallen while the incidence of lung adenocarcinoma (LUAD) has risen over the last few decades. This is due to decreased smoking rates and changes in cigarette filtering and composition [1]. Lung SCC remains a common malignancy overall, accounting for approximately 85,000 new cases in the United States each year and over 400,000 worldwide [2]. The situation in Latin-American countries is not different, approximately 75,000 new cases of lung cancer are diagnosed yearly. Lung cancer is a public health problem, and squamous cell carcinoma (SCC) is the second most prevalent subtype of this neoplasm. We sought to characterize the SCC genomic profile using a validated Generation Sequencing (NGS) platform
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