scholarly journals SMARCA4/BRG1–Deficient Non–Small Cell Lung Carcinomas: A Case Series and Review of the Literature

2020 ◽  
Vol 145 (1) ◽  
pp. 90-98 ◽  
Author(s):  
Aruna Nambirajan ◽  
Varsha Singh ◽  
Nishu Bhardwaj ◽  
Saurabh Mittal ◽  
Sunil Kumar ◽  
...  
Keyword(s):  
Case Series ◽  
Growth Factor Receptor ◽  
Large Cell ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Lung Carcinomas ◽  
Anaplastic Lymphoma ◽  
Thyroid Transcription Factor 1 ◽  
Poorly Differentiated

Context.— Somatic mutations in SMARCA4 (SWI/SNF–related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4) gene and/or BRG1 (Brahma-related gene 1) loss identifies a subset of non–small cell lung carcinomas (NSCLCs) lacking alterations in EGFR (epidermal growth factor receptor), ALK (anaplastic lymphoma kinase), and ROS1 (ROS proto-oncogene 1) genes. Preliminary observations suggest responsiveness to immunotherapy and targeted therapies. Objective.— To study BRG1 loss in NSCLCs and elucidate the clinicopathologic profile of such SMARCA4-deficient NSCLCs. Design.— Non–small cell lung carcinomas diagnosed during 6 years were subject to immunohistochemistry for BRG1 and BRM (Brahma). Tumors with BRG1 loss were stained with antibodies against thyroid transcription factor 1 (TTF-1), p40, cytokeratins, hepatocyte paraffin 1 (Hep Par 1), Sal-like protein 4 (SALL4), CD34, SRY-box 2 (SOX2), chromogranin, synaptophysin, p53, integrase interactor 1, ALK, and ROS1. EGFR mutation testing was performed by polymerase chain reaction–based method. Results.— Among 100 NSCLCs tested, 4 cases (4%) showed BRG1 loss. The histology ranged from solid adenocarcinomas (n = 1) to large cell/poorly differentiated carcinomas (n = 3) with clear cell cytology in 2 cases. All showed loss/reduction of BRM with variable cytokeratin and SALL4 expression, and were negative for TTF-1, p40, Hep Par 1, ALK, ROS1, and EGFR mutations. CD34 and SOX2 were negative in all 4 cases. Isolated BRM loss was common (21%), distributed across all NSCLC subtypes including squamous cell carcinomas and a hepatoid adenocarcinoma. Conclusions.— BRG1 loss occurs in a subset of TTF-1/p40–negative poorly differentiated NSCLCs. Identification and follow-up will clarify the prognosis, diagnostic criteria, and potential for therapeutic personalization.

scholarly journals Alectinib activity in chemotherapy-refractory metastatic RET-rearranged non-small cell lung carcinomas: A case series

Lung Cancer ◽  
2020 ◽  
Vol 139 ◽  
pp. 9-12 ◽  
Author(s):  
Maurício Fernando Silva Almeida Ribeiro ◽  
João Victor Machado Alessi ◽  
Leandro Jonata Carvalho Oliveira ◽  
Aline Bobato Lara Gongora ◽  
Karina Perez Sacardo ◽  
...  
Keyword(s):  
Case Series ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Carcinomas

First-Line Gefitinib for Patients With Advanced Non–Small-Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutations Without Indication for Chemotherapy

2009 ◽  
Vol 27 (9) ◽  
pp. 1394-1400 ◽  
Author(s):  
Akira Inoue ◽  
Kunihiko Kobayashi ◽  
Kazuhiro Usui ◽  
Makoto Maemondo ◽  
Shoji Okinaga ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Nucleic Acid ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
First Line ◽  
Epidermal Growth

Purpose This multicenter phase II study was undertaken to investigate the efficacy and feasibility of gefitinib for patients with advanced non–small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations without indication for chemotherapy as a result of poor performance status (PS). Patients and Methods Chemotherapy-naïve patients with poor PS (patients 20 to 74 years of age with Eastern Cooperative Oncology Group PS 3 to 4, 75 to 79 years of age with PS 2 to 4, and ≥ 80 years of age with PS 1 to 4) who had EGFR mutations examined by the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method were enrolled and received gefitinib (250 mg/d) alone. Results Between February 2006 and May 2007, 30 patients with NSCLC and poor PS, including 22 patients with PS 3 to 4, were enrolled. The overall response rate was 66% (90% CI, 51% to 80%), and the disease control rate was 90%. PS improvement rate was 79% (P < .00005); in particular, 68% of the 22 patients improved from ≥ PS 3 at baseline to ≤ PS 1. The median progression-free survival, median survival time, and 1-year survival rate were 6.5 months, 17.8 months, and 63%, respectively. No treatment-related deaths were observed. Conclusion This is the first report indicating that EGFR mutation-positive patients with extremely poor PS benefit from first-line gefitinib. Because there previously has been no standard treatment for these patients with short life expectancy other than best supportive care, examination of EGFR mutations as a biomarker is recommended in this patient population.

Epidermal Growth Factor Receptor Mutations in Plasma DNA Samples Predict Tumor Response in Chinese Patients With Stages IIIB to IV Non–Small-Cell Lung Cancer

2009 ◽  
Vol 27 (16) ◽  
pp. 2653-2659 ◽  
Author(s):  
Hua Bai ◽  
Li Mao ◽  
hang Shu Wang ◽  
Jun Zhao ◽  
Lu Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Egfr Mutation ◽  
Tumor Response ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Plasma Samples ◽  
Plasma Dna ◽  
Small Cell Lung ◽  
Epidermal Growth

Purpose Mutations in the epidermal growth factor receptor (EGFR) kinase domain can predict tumor response to tyrosine kinase inhibitors (TKIs) in non–small-cell lung cancer (NSCLC). However, obtaining tumor tissues for mutation analysis is challenging. We hypothesized that plasma-based EGFR mutation analysis is feasible and has value in predicting tumor response in patients with NSCLC. Patients and Methods Plasma DNA samples and matched tumors from 230 patients with stages IIIB to IV NSCLC were analyzed for EGFR mutations in exons 19 and 21 by using denaturing high-performance liquid chromatography. We compared the mutations in the plasma samples and the matched tumors and determined an association between EGFR mutation status and the patients' clinical outcomes prospectively. Results In 230 patients, we detected 81 EGFR mutations in 79 (34.3%) of the patients' plasma samples. We detected the same mutations in 63 (79.7%) of the matched tumors. Sixteen plasma (7.0%) and fourteen tumor (6.1%) samples showed unique mutations. The mutation frequencies were significantly higher in never-smokers and in patients with adenocarcinomas (P = .012 and P = .009, respectively). In the 102 patients who failed platinum-based treatment and who were treated with gefitinib, 22 (59.5%) of the 37 with EGFR mutations in the plasma samples, whereas only 15 (23.1%) of the 65 without EGFR mutations, achieved an objective response (P = .002). Patients with EGFR mutations had a significantly longer progression-free survival time than those without mutations (P = .044) in plasma. Conclusion EGFR mutations can be reliably detected in plasma DNA of patients with stages IIIB to IV NSCLC and can be used as a biomarker to predict tumor response to TKIs.

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