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Published on: June 13, 2019
Molecular characterization of pulmonary sarcomatoid carcinoma: analysis of 33 cases
Simone Bsp Terra1, Jin S Jang1, Lintao Bi1
1Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
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.
Insights
Pulmonary sarcomatoid carcinomas harbor targetable genetic mutations, including TP53 and KRAS. Testing for these abnormalities may guide treatment with targeted therapies or clinical trials for patients.
Area of Science:
- Oncology
- Genetics
- Pulmonary Medicine
Background:
- Targetable genetic alterations are common in lung adenocarcinoma, driving targeted therapy advancements.
- Molecular landscape and targetable mutations in pulmonary sarcomatoid carcinomas (PSCs) remain largely uncharacterized.
Purpose of the Study:
- To investigate the spectrum of targetable genetic alterations in PSCs.
- To identify potential therapeutic targets for PSC patients.
Main Methods:
- Comprehensive genomic profiling of approximately 2800 mutations across 50 oncogenes and tumor suppressors in 33 PSCs.
- Analysis included targeted gene sequencing and ALK (Anaplastic Lymphoma Kinase) assessment via immunohistochemistry and FISH.
Main Results:
- 72% of PSCs (24/33) harbored at least one genetic abnormality.
- TP53 mutations (58%) and KRAS mutations (30%) were the most frequent.
- One case exhibited ALK gene rearrangement, and four tumors had mutations in genes with experimental therapies (BRAF, NRAS, PIK3CA, AKT1).
Conclusions:
- PSCs possess a significant number of targetable genetic alterations.
- Testing for these mutations is recommended to identify patients who may benefit from existing targeted therapies or novel treatment options in clinical trials.
