PSC subtyping based on TTF‐1 and p40 expression reveals distinct molecular characteristics and therapeutic strategies

Abstract

Pulmonary sarcomatoid carcinoma (PSC) is a unique form of poorly differentiated nonsmall cell lung cancer (NSCLC) and is notorious for its highly malignant nature and dismal prognosis. To introduce effective treatment for PSC patients, precise subtyping of PSC is demanding. In our study, TTF-1 and P40 immunohistochemistry (IHC) staining were applied to 56 PSC patients with multiomics data. According to IHC results, we categorized these patients into three subgroups and profiled their molecular contexture using bioinformatic skills. IHC results classified these patients into three subgroups: TTF-1 positive subgroup (n = 27), P40 positive subgroup (n = 15) and double-negative subgroup (n = 14). Spindle cell samples accounted for 35.71% (5/14) of double-negative patients, higher than others (P = .034). The three subgroups were heterogeneous in the genomic alteration spectrum, showing significant differences in the RTK/RAS pathway (P = .004) and the cell cycle pathway (P = .030).The methylation profile of the double-negative subgroup was between the other two subgroups. In similarity analysis, the TTF-1 and p40 subgroups were closely related to LUAD and LUSC, respectively. The TTF-1 positive subgroup had the highest leukocyte

18F-FDG PET/CT imaging in pulmonary sarcomatoid carcinoma

“…TTF-1 is often expressed unexpectedly in a large number of cases of PSC. A multi-omics study ( 15 ) based on TTF-1 and P40 immunohistochemistry (IHC) established a new PSC typing method that was simpler and more economical than genotyping. they divided PSC patients into three subtypes (TTF-1 positive group, P40 positive group, and double negative group).…”

Targeted therapy for rare lung cancers: Status, challenges, and prospects

“…EGFR mutations were found in 5.0%–22.6% of patients with PSC. 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 Liu et al. 83 reckoned EGFR -sensitizing mutations as one of the trunk mutations in PSC despite high intratumor heterogeneity (ITH).…”

“…METex14 skipping mutations were detected in 2.0%–31.8% of PSC, which was more frequent than that of other NSCLC subtypes. 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 89 , 90 , 91 Several retrospective studies of patients with METex14 -positive lung cancer, including PSC patients, reported a partial response to first-line crizotinib, a multitargeted TKI covering MET. 92 , 93 In addition, an open-label, phase 2 clinical trial of tepotinib, a highly selective MET TKI, enrolled two PSC patients out of 152 in total, with an ORR of 46% and a median duration of response of 11.1 months.…”

“…KRAS mutations were identified in 14.6%–39.0% of PSC patients, 78 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 89 , 90 , 99 , 100 while neither retrospective studies nor prospective studies are available. Notably, KRAS mutations were reported to have a positive relationship with TMB and PD-L1 expression (p = 0.031), 101 and KRAS-mutated cases had a higher response rate of pembrolizumab.…”