title: Molecular characterization of pulmonary sarcomatoid carcinoma: analysis of 33 cases.
abstract: Several targetable genetic alterations have been found in lung cancer, predominantly in adenocarcinomas, which have led to important therapeutic advancements with the advent of targeted therapy. In contrast, the molecular features and presence of targetable genetic abnormalities in pulmonary sarcomatoid carcinomas are largely unknown. Thirty-three cases of pulmonary sarcomatoid carcinoma were tested for approximately 2800 mutations in 50 oncogenes and tumor-suppressor genes, including EGFR, KRAS, NRAS, TP53, BRAF, ERBB2, JAK3, AKT1, ATM, MET, KIT, and PIK3CA. ALK immunostaining was performed, and ALK FISH was performed on cases with any degree of staining. Twenty-four of the 33 cases (72%) had at least one genetic abnormality: 19 cases (58%) had TP53 mutations; 10 cases (30%) had KRAS mutations; AKT1, JAK3, BRAF, NRAS, and PIK3CA mutations were observed in 1 case each (3%). Six of the 19 cases (32%) with a mutation in TP53 had simultaneous mutations in KRAS (18%). The cases with alterations in JAK3, BRAF, and NRAS also had mutations in TP53. The case showing a mutation in PIK3CA had a mutation in KRAS. No EGFR mutations were observed. One case had ALK gene rearrangement. ALK rearrangement was observed in a single case of sarcomatoid carcinoma (3%), which has currently available targeted therapy. Four tumors had mutations in genes with experimental molecular-based therapy, including BRAF, NRAS, PIK3CA, and AKT1. Testing for targetable mutations should be considered for patients with pulmonary sarcomatoid carcinoma, as a subset may benefit from currently approved drugs or clinical trials of novel therapeutic options available for other types of lung cancer.
authors.affiliation: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Simone Bsp
authors.initials: SB
authors.lastname: Terra
authors.affiliation: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Jin S
authors.initials: JS
authors.lastname: Jang
authors.affiliation: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Lintao
authors.initials: L
authors.lastname: Bi
authors.affiliation: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Kipp
authors.affiliation: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Jen
authors.affiliation: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Eunhee S
authors.initials: ES
authors.lastname: Yi
authors.affiliation: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Boland
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D002296:Carcinosarcoma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D058990:Molecular Targeted Therapy; D009154:Mutation; D010641:Phenotype; D011237:Predictive Value of Tests; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor