Synchronous lung cancers from 60 patients (42 with adenocarcinoma and 18 with squamous cell carcinoma), clinically considered to represent intrapulmonary metastases, were histologically subtyped according to the 2015 World Health Organization classification of lung tumors and subjected to genotypic analysis (KRAS, EGFR, BRAF, PIK3CA, ALK, MET and ROS1 in adenocarcinoma and PIK3CA and p16 in squamous cell carcinoma).
Our findings provide evidence that ALK or ROS1 translocations are crucial events in tumourigenesis of pulmonary adenocarcinoma of very young patients, including pediatric patients.
Although the MET gene amplification and ROS1 gene fusion in NSCL adenocarcinoma were low-probability events, detection of the gene status of EGFR, ROS1, and MET will facilitate screening more NSCL adenocarcinoma patients who might benefit from targeted therapy.
ROS1 rearrangements were detected in 1.8% of patients with resected NSCLC and were detected exclusively in adenocarcinomas, which is similar to the frequency detected in non-Asian patients.
This review summarizes the hot topics of immunohistochemistry in lung cancer, including (i) adenocarcinoma vs squamous cell carcinoma; (ii) neuroendocrine markers; (iii) ALK, ROS1, and EGFR; (iv) PD-L1 (CD274); (v) lung carcinoma vs malignant mesothelioma; and (vi) NUT carcinoma.
Three biomarker-specified groups of advanced lung adenocarcinomas can now be defined, each paired with a specific palliative first-line systemic therapy of proven clinical benefit: (1) EGFR/ALK/ROS1-affected adenocarcinoma paired with a matched tyrosine kinase inhibitor (∼20% of cases), (2) PD-L1-enriched adenocarcinoma (TPS ≥50%) paired with anti-PD-1 pembrolizumab (∼30% of cases), and (3) biomarker-negative (i.e., EGFR/ALK/ROS1/PD-L1-negative) adenocarcinoma paired with platinum doublet chemotherapy with or without bevacizumab (∼50% of cases).