Association of EGFR mutation or ALK rearrangement with expression of DNA repair and synthesis genes in never-smoker females with pulmonary adenocarcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10527-10527
Author(s):  
Xiaoxia Chen ◽  
Shengxiang Ren ◽  
Peng Kuang ◽  
ChunXia Su ◽  
Jiayu Li ◽  
...  
Keyword(s):  
Dna Repair ◽  
Mrna Expression ◽  
Egfr Mutation ◽  
Excision Repair ◽  
Egfr Mutations ◽  
Mrna Levels ◽  
Alk Rearrangement ◽  
Anaplastic Lymphoma ◽  
Alk Positive ◽  
Nsclc Patients

10527 Background: Epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement was found not only predict the efficacy of targeted drugs, but also associate with the efficacy of chemotherapy drugs in non-small cell lung cancer (NSCLC) patients. We investigated the relationship of EGFR mutation status or ALK rearrangement and DNA repair or synthesis genes, such as excision repair cross-complementing 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1), thymidylate synthetase (TS) and breast cancer gene one (BRCA1) gene expression, as a potential explanation for these observations. Methods: In this surgical series, 104 resected lung adenocarcinomas from nonsmoker females were analyzed concurrently for the EGFR mutation, ALK rearrangement status and mRNA expression of ERCC1, RRM1, TS and BRCA1 genes. EGFR mutation detection was performed by the method of ADx-ARMS, ALK rearrangement was detected by PCR and the mRNA expression of different genes were tested using the method of real-time PCR. Results: 73 (70.2%) patients harbored EGFR mutations and 10 (9.6%) had ALK rearrangement. The ERCC1 mRNA level in patients with EGFR mutation was 3.44±1.94×10-3 , which is significantly lower than in the patients with ALK positive and both negative(4.60±1.95×10-3 and 4.95±2.33×10-3 respectively, P=0.010). While the TS mRNA levels were significantly lower in the patients with EGFR mutation(1.15±1.38×10-3 VS 2.69±3.97×10-3, P=0.006) or ALK positive (1.21±0.78×10-3VS 2.69±3.97×10-3, P=0.020) than in patients with both negative. Conclusions: NSCLC specimens harboring activating EGFR mutations are more likely to express low ERCC1 and TS mRNA levels, while NSCLC patients with ALK rearrangement are more likely to express low TS mRNA levels, which could be helpful to select a proper chemotherapy regimen for NSCLC patients with known EGFR mutation or ALK fusion status.

Two different patterns of lung adenocarcinoma with concomitant EGFR mutation and ALK rearrangement

2021 ◽  
pp. 030089162110055
Author(s):  
Dashi Zhao ◽  
Jun Fan ◽  
Li Peng ◽  
Bo Huang ◽  
Yili Zhu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Alk Rearrangement ◽  
Molecular Alterations ◽  
Anaplastic Lymphoma ◽  
Sporadic Cases ◽  
Epidermal Growth ◽  
Rare Group

Epidermal growth factor receptor ( EGFR) mutations and anaplastic lymphoma kinase ( ALK) rearrangements are considered mutually exclusive in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma (LUAC). However, sporadic cases harboring concomitant EGFR and ALK alterations have been increasingly reported. There is no consensus opinion regarding the treatment of patients positive for both molecular alterations. NSCLC with EGFR/ ALK coalterations should be separated into two subtypes: unifocal and multifocal LUAC. Here, we present an overview of the available literature regarding this rare group of patients to provide useful suggestions for therapeutic strategies.

Epidemiology of PD-L1 and ALK expression and EGFR mutational status in Argentinian patients with lung cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20565-e20565 ◽  
Author(s):  
Ruben Salanova ◽  
Julio C Calderazzo Pereyra ◽  
Laura Leguina ◽  
Asuncion Bena ◽  
Mariana Barberis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Egfr Mutation ◽  
Egfr Mutations ◽  
Alk Rearrangement ◽  
Lung Cancer Patients ◽  
Mutational Status ◽  
Alk Positive ◽  
Egfr Mutant ◽  
Exon 19

e20565 Background: Until now, the results of the correlation between PD-L1, ALK expression and EGFR mutations remain controversial. We prospectively evaluated patterns among EGFR mutant, ALK positive and PD-L1 positive lung cancer patients. Methods: PD-L1 and ALK expression was evaluated in 342 adenocarcinomas (AD) of the lung using inmunohistochemestry (anti-PD-L1 22C3, anti-ALK D5F3), and EGFR mutations using real time PCR (therascreen EGFR RGQ PCR Kit version 2). PD-L1 was also evaluated in 36 squamous (SQ) cell carcinomas. Results: 181 of 342 patients with AD were positive for PD-L1. 108 were positive with a TPS value between 1 and 49, and 73 were positive with a TPS value higher than 50 (p = 0.002). 25 of 36 patients with SQ were positive for PD-L1. 17 were positive with a TPS value between 1 and 49, and 8 were positive with a TPS value higher than 50. 133 samples with AD PD-L1 positive and 97 PD-L1 negative were tested for EGFR and ALK, 33 and 14 respectively were positive for EGFR mutations (p = 0.15), with 45% for exon 19 deletions (p = 0.003), 5 and 0 respectively were positive for ALK translocations (p = 0.053). 210 of 342 patients were men and 132 were women, 117 and 64 were positive for PD-L1 expression respectively (p > 0.1). Conclusions: NSCLC with EGFR mutation showed a trend for higher frequency of positive PD-L1 expression and NSCLC harboring ALK rearrangement was significantly associated with PD-L1 expression. These findings might contribute to the understanding of the regulation of PD-L1 expression in lung cancer and its relation to ALK expression and EGFR mutation.

Triple probe FISH approach for detecting EML4-ALK gene rearrangement in Chinese patients with NSCLC.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21080-e21080
Author(s):  
Weimin Mao ◽  
Mark Han ◽  
Zhiqiang Ling ◽  
Wenyong Sun ◽  
Gu Zhang ◽  
...  
Keyword(s):  
Chinese Patients ◽  
Alk Rearrangement ◽  
Anaplastic Lymphoma ◽  
Unselected Patient ◽  
Dual Color ◽  
Alk Positive ◽  
Novel Target ◽  
Nsclc Patients ◽  
First Time

e21080 Background: The echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion represents a novel target for the therapy of a subset of non-small cell lung cancer (NSCLC). ALK rearrangement has been found in approximately 1.6–11.6% of NSCLC in unselected patient populations, but the frequency also varied when different diagnostic approach was used. We, for the first time, investigated frequency of EML4-ALK rearrangement in unselected Chinese patients with NSCLC using recent developed fluorescence in situ hybridization (FISH) triple color break-apart probe. Methods: One hundred-thirty one FFPE specimens from NSCLC patients were collected for the investigation. Fusion between 3’ portion of ALK gene and the 5’ portion of EML4 gene was detected using FISH tri-check probe (ZytoVision, Germany). Positive cells were defined as having any signal A ( distance more than two-time the ALK signal size) or signal B ( distance between one- and two-time the ALK signal size plus EML4 translocation signal) or any isolated ALK 3’ signal. Total 100 nuclei for each specimen were counted. Specimen was as classified as EML4-ALK rearrangement when the proportion of positive cells was over 15%. ALK/EML4 signals over 6 in over 10% nuclei were classified as gene amplification. Results: Of 131 specimens, frequency of ALK rearrangement was 10.7% (14/131) when positive cells were counted by signal A and isolated ALK 3’ signal (dual color). Frequency of EML4-ALK rearrangement was 13.0% (17/131) when positive cells were counted by signal A, B and isolated ALK 3’ signal (triple color), in which 21% (17/14) more cases were classified as EML4-ALK rearrangement comparing dual color enumeration. ALK and EML4 amplification were observed in 2.3% (3/131) specimens, respectively, in which two were co-amplified and none of them had EML4-ALK rearrangement. Conclusions: Present result showed that frequency of EML4-ALK rearrangement in unselected Chinese patients with NSCLC was 13.0% determined by FISH tri-check probe. This study suggested that counting both ALK inversion and EML4 translocation may contribute to defining EML4-ALK positive cells.

Efficacy and Biomarkers of Advanced Non-small Cell Lung Carcinoma (NSCLC) Patients Receiving Different PD-1 Agents in Northern China: A Real-world Clinical Study

2020 ◽  
Author(s):  
Man Jiang ◽  
Xiaochun Zhang
Keyword(s):  
Real World ◽  
Tp53 Mutation ◽  
Small Cell Lung Carcinoma ◽  
Objective Response ◽  
Egfr Mutations ◽  
Alk Rearrangement ◽  
Cell Lung Carcinoma ◽  
Anaplastic Lymphoma ◽  
Potential Biomarker ◽  
Nsclc Patients

Abstract Aim and Methods: From May 2019 to January 2020, 116 advanced NSCLC patients with programmed death ligand-1 (PD-L1) expression > 1% were treated with nivolumab (44), pembrolizumab (21), and toripalimab (51) as a mono-therapy, respectively. The primary endpoints were defined as the objective response rate (ORR) after 3 and 6 months of therapy, and the progression-free survival (PFS). The observed efficacy of the different PD-1 antibodies was also compared. The gene mutation statuses of tumor protein p53 (TP53), epidermal growth factor receptor ( EGFR ), and anaplastic lymphoma kinase ( ALK ), the tumor mutational burden (TMB), along with the expression of CD47 were analyzed.Results: Toripalimab had a higher ORR and a longer PFS than the other two PD-1 agents after 3 months of evaluation (P = 0.0178). Thenon-classical mutations of EGFR (EGFRG719C and EGFRE709V) did not significantly influence the efficacy of the PD-1 inhibitors, while TP53 mutation, high TMB and elevated PD-L1 expression showed benefits. EGFR co-mutated genes were enriched in the “Response to osmotic stress” , “response to oxidative stress” and “myeloid leukocyte activation” pathways. CD47 expression showed a negative correlation to the prognosis of anti-PD-1 therapy. Participants with ALK rearrangement exhibited poor clinical outcomes. Conclusions: Toripalimab seemed to have a more rapid effect and provide a longer PFS than pembrolizumab and nivolumab. The PD-1 blockade therapy was benefited by TP53 mutation, high TMB, and elevated PD-L1 expression. CD47 expression is a potential biomarker to predict the efficacy of PD-1 blockade treatment in patients with EGFR mutations.Clinical Trail : Real-World Study of Four PD-1 Agents in China(May/22/2019)Trial Registration number: NCT03966456 URL:https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0008Y4C&selectaction=Edit&uid=U00045OC&ts=3&cx=z2uldc

Differences in utilization of ALK rearrangement FISH analysis and EGFR assay.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18067-e18067
Author(s):  
Christopher S. Lathan ◽  
Julie Ann Lynch
Keyword(s):  
Incidence Rate ◽  
Diagnostic Test ◽  
Egfr Mutation ◽  
Penetration Rate ◽  
Egfr Mutations ◽  
Fish Analysis ◽  
Alk Rearrangement ◽  
Regional Factors ◽  
Public Datasets ◽  
Nsclc Patients

e18067 Background: This study examined institutional and regional factors associated with use of ALK rearrangement FISH diagnostic test compared to the EGFR assay. Previous research presented at AACR Cancer Disparities conference illustrated substantial underutilization of the EGFR assay. Disparities existed in access by institutional and regional factors. Methods: We linked proprietary industry data for clinical diagnostic assays (EGFR mutation and ALK rearrangement) provided by Genzyme Genetics and Abbott Molecular to public datasets which provided institutional and regional characteristics of US hospitals. Individual orders were aggregated and summarized to the hospital. Each hospital’s Medicare provider number (known as the OSCAR number) was obtained and recorded. OSCAR number and zip code were used to link the proprietary and public datasets. Public datasets included Census files, CMS/NCI Provider of Service (POS) files, among others, all current as of 2011. Logistic and multiple regression analysis were conducted. Results: Initial analysis of data suggests higher utilization of the ALK rearrangement FISH analysis when compared to EGFR Assay. However, even with incorporation of both assays into clinical practice guidelines, significant institutional and regional differences existed in access to tumor tissue analysis. 7800 EGFR assay tests were sold in 2010. First 5 months post approval; approximately 12,000 Vysis tests were sold. A reasonable approximation of the testable population of NSCLC patients, given histology and tissue availability is approximately 114,000 patients. This suggests a 7% penetration rate for the EGFR mutation analysis and a 10% penetration rate for ALK rearrangement assay, though EGFR mutations have a 15% incidence rate compared to 5% incidence rate of EML-ALK4 rearrangement. Conclusions: Uptake of the ALK rearrangement assay is likely higher due to the linkage of crizotinib to the FISH diagnostic test. Utilization patterns show regional underutilization that could contribute to disparities.

scholarly journals EML4-ALK positive lung adenocarcinoma with skeletal muscle metastasis in the right calf which was treatable with lorlatinib after resistance to treatment with alectinib

2021 ◽  
Vol 14 (4) ◽  
pp. e240295
Author(s):  
Hironari Matsuda ◽  
Munechika Hara ◽  
Shin-Ichiro Iwakami ◽  
Kazuhisa Takahashi
Keyword(s):  
Skeletal Muscle ◽  
Lung Adenocarcinoma ◽  
Kinase Inhibitor ◽  
Stable Condition ◽  
Japanese Woman ◽  
Alk Rearrangement ◽  
Anaplastic Lymphoma ◽  
Resistance To Treatment ◽  
Alk Positive ◽  
The Right

This report concerns a patient with skeletal muscle metastases due to lung adenocarcinoma harbouring an echinoderm microtubule-associated protein-like-4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangement, who was successfully treated with lorlatinib after resistance to alectinib. A right lower lobectomy based on a diagnosis of lung adenocarcinoma was performed on a 77-year-old Japanese woman. After 7 months of surgical resection, a mass in the right calf was observed. A fine-needle aspiration biopsy from the mass was performed and the mass was diagnosed as metastatic adenocarcinoma harbouring EML4-ALK rearrangement. Alectinib was administered for 10 months. Then, administration of lorlatinib, an ALK tyrosine kinase inhibitor classified as third generation, was initiated after resistance to treatment with alectinib. After starting treatment with lorlatinib, the gastrocnemius tumour diminished and has maintained a stable condition. Our case suggests that EML4-ALK positive lung adenocarcinoma is treatable with lorlatinib after resistance to treatment with alectinib.

scholarly journals Frequency of EGFR Mutation and EML4-ALK fusion gene in Arab Patients with Adenocarcinoma of the Lung

2015 ◽  
Vol 6 (2) ◽  
pp. 19-23
Author(s):  
Hanan Ezzat Shafik ◽  
Mohamed Ashour
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egfr Mutation ◽  
Fusion Gene ◽  
Receptor Gene ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Anaplastic Lymphoma ◽  
Epidermal Growth

Abstract Introduction: Improvement in the clinical outcome of lung cancer is likely to be achieved by identification of the molecular events that underlie its pathogenesis. The frequency of epidermal growth factor receptor (EGFR) mutations is ethnicity-dependent, with a higher proportion in Asian populations than in whites, while the incidence of EML4-ALK (echinoderm microtubule-associated-protein like 4-anaplastic lymphoma kinase) fusion gene ranged from 1.6% to 16.4% in patients with NSCLC and these individuals were distinct from those harbouring mutations in the epidermal growth factor receptor gene. This study was conducted to determine the frequency of EGFR mutation and EML4-ALK fusion gene in our population and to determine the effect of different clinicopathological features on the expression of those mutations in patients with lung adenocarcinoma. Results: EGFR mutations were detected in approximately 33% of our patients in this series; the most frequently detected mutation was exon 19 deletion. EML4-ALK fusion gene was detected in 7.3% of patients. Conclusion: Our population exhibited the incidence of EGFR mutation approximately similar to that reported in East Asia and Japanese patients, higher than that recorded in USA, and Australia. However, more studies with larger patients’ numbers are needed to verify this finding.

Sign in / Sign up

Export Citation Format

Share Document