EML4-ALK-gene rearrangement comparative analysis in circulating tumor cells and in tumor tissue of patients with lung adenocarcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7591-7591
Author(s):  
Marius Ilie ◽  
Elodie Long ◽  
Catherine Butori ◽  
Veronique Hofman ◽  
Celine Coelle ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Gene Rearrangement ◽  
Alk Rearrangement ◽  
Molecular Subgroup ◽  
Non Invasive ◽  
Tumor Tissues ◽  
Gene Status

7591 Background: The implementation of new theranostic biomarkers in Oncology is leading to impressive therapeutic improvements. In patients with lung cancer, the possibility to use Circulating Tumor Cells (CTCs) as a non-invasive theranostic approach is a clinically appealing challenge. Adenocarcinomas with EML4-ALK rearrangement are a new molecular subgroup of lung tumors with very good response to Crizotinib, an ALK inhibitor. We have thus aimed at developing an informative assay characterizing the ALK-gene status in CTCs isolated from patients with lung cancer. Methods: CTCs were isolated preoperatively using Isolation by Size of Epithelial Tumor cells method (ISET) from 65 patients with lung adenocarcinoma and blindly screened for ALK-gene status. ALK break-apart fluorescence in situ hybridization (FISH) (LSI ALK dual colour probes set) and immunochemistry using an anti-ALK antibody (5A4 clone) were blindly performed on CTCs and corresponding tumor tissues and results were compared. Results: Two patients consistently showed ALK-gene rearrangement and strong ALK protein expression in CTCs and corresponding tumor samples. Negative results (both ALK FISH and ALK immunochemistry) were found in CTCs and corresponding tumor samples from the other 63 patients. Conclusion: We have developed an approach allowing to characterize ALK-gene status in CTCs from patients with lung cancer and shown consistent results in CTC and tumor tissues. These preliminary results encourage larger studies and open new avenues for non-invasive, real-time, theranostic monitoring of cancer patients.

Detection of Circulating Tumor Cells Harboring a Unique ALK Rearrangement in ALK-Positive Non–Small-Cell Lung Cancer

2013 ◽  
Vol 31 (18) ◽  
pp. 2273-2281 ◽  
Author(s):  
Emma Pailler ◽  
Julien Adam ◽  
Amélie Barthélémy ◽  
Marianne Oulhen ◽  
Nathalie Auger ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Alk Rearrangement ◽  
Mesenchymal Phenotype ◽  
Alk Positive ◽  
Tumor Biopsies

Purpose The diagnostic test for ALK rearrangement in non–small-cell lung cancer (NSCLC) for crizotinib treatment is currently done on tumor biopsies or fine-needle aspirations. We evaluated whether ALK rearrangement diagnosis could be performed by using circulating tumor cells (CTCs). Patients and Methods The presence of an ALK rearrangement was examined in CTCs of 18 ALK-positive and 14 ALK-negative patients by using a filtration enrichment technique and filter-adapted fluorescent in situ hybridization (FA-FISH), a FISH method optimized for filters. ALK-rearrangement patterns were determined in CTCs and compared with those present in tumor biopsies. ALK-rearranged CTCs and tumor specimens were characterized for epithelial (cytokeratins, E-cadherin) and mesenchymal (vimentin, N-cadherin) marker expression. ALK-rearranged CTCs were monitored in five patients treated with crizotinib. Results All ALK-positive patients had four or more ALK-rearranged CTCs per 1 mL of blood (median, nine CTCs per 1 mL; range, four to 34 CTCs per 1 mL). No or only one ALK-rearranged CTC (median, one per 1 mL; range, zero to one per 1 mL) was detected in ALK-negative patients. ALK-rearranged CTCs harbored a unique (3′5′) split pattern, and heterogeneous patterns (3′5′, only 3′) of splits were present in tumors. ALK-rearranged CTCs expressed a mesenchymal phenotype contrasting with heterogeneous epithelial and mesenchymal marker expressions in tumors. Variations in ALK-rearranged CTC levels were detected in patients being treated with crizotinib. Conclusion ALK rearrangement can be detected in CTCs of patients with ALK-positive NSCLC by using a filtration technique and FA-FISH, enabling both diagnostic testing and monitoring of crizotinib treatment. Our results suggest that CTCs harboring a unique ALK rearrangement and mesenchymal phenotype may arise from clonal selection of tumor cells that have acquired the potential to drive metastatic progression of ALK-positive NSCLC.

scholarly journals P2.01-060 Comparative Analysis of PD-L1 Expression between Circulating Tumor Cells and Tumor Tissues in Patients with Lung Cancer

2017 ◽  
Vol 12 (1) ◽  
pp. S822-S823
Author(s):  
Yasuhiro Koh ◽  
Satomi Yagi ◽  
Hiroaki Akamatsu ◽  
Ayaka Tanaka ◽  
Kuninobu Kanai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Comparative Analysis ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Tumor Tissues

Consistency evaluation of lung adenocarcinoma tissue and circulating tumor cells related gene mutation detection based on multi-site immunomagnetic beads

2022 ◽  
pp. 088532822110658
Author(s):  
Keying Xue ◽  
Bingqing Luo ◽  
Xiaoqing Li ◽  
Weixian Deng ◽  
Chunyan Zeng ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Lung Adenocarcinoma ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Targeted Therapies ◽  
Sanger Sequencing ◽  
Gene Mutations ◽  
Genetic Mutations ◽  
Separation System ◽  
Tumor Tissues

This study was designed to investigate the feasibility of genetic testing using circulating tumor cells (CTCs) instead of tumor tissues in lung adenocarcinoma to break through its limitation. Separation system for epithelial cell adhesion molecule (EpCAM), epidermal growth factor receptor (EGFR), and Vimentin expressing CTCs was constructed and used to capture CTCs in the blood samples of 57 patients with lung adenocarcinoma. Genetic mutations of genes involved in targeted therapies were detected by next-generation sequencing (NGS) in tissues from these patients. Blood CTC samples with the gene mutations identified by tissue-NGS were selected and corresponding gene mutations were detected by Sanger sequencing. The specificity of the CTC separation system was 95.48% and the sensitivity was 90.85%. The average number of CTCs in the blood of patients with lung adenocarcinoma was 12.47/7.5 mL. Comparison of the tissue-NGS with the CTC-Sanger sequencing showed that the consistencies of genetic mutations of EGFR ( n = 24), KRAS ( n = 9), TP53 ( n = 19), BRAF ( n = 1), ERBB2 ( n = 2), and PIK3CA ( n = 3) were 92.31%, 75.00%, 86.36%, 50.00%, 66.67%, and 75.00%, with an overall consistency of 84.06%. The CTC separation system established in this study shows high specificity and sensitivity. CTCs can be used as a suitable alternative to tumor tissues that are difficult to obtain in clinical practice and overcome the difficulties in tumor tissue collection, which is of significance in guiding clinical medication and individualized treatment with significant clinical application value in terms of genetic testing for targeted therapies in tumor treatment.

scholarly journals Effect of Napsin A and Circulating Tumor Cells with Mesenchymal Phenotype in Lung Adenocarcinoma

2021 ◽  
Author(s):  
Yu Hong Wei ◽  
yi Zhi He
Keyword(s):  
Lung Adenocarcinoma ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Tumor Stage ◽  
Free Survival ◽  
Mesenchymal Phenotype ◽  
Napsin A ◽  
Tumor Tissues ◽  
Positive Rate ◽  
Degree Of Differentiation

Abstract Objective: To evaluate the clinical significance of Napsin A and circulating tumor cells（CTCs）with mesenchymal phenotype (M-CTC) in lung adenocarcinoma(LUAD).Materials and Methods: Clinical data of 97 LUAD patients were retrieved. The CanPatrolTM CTC enrichment platform was used to isolate CTCs from the peripheral blood of LUAD patients. The protein expression of Napsin A in the tumor tissues was analyzed by immunohistochemistry. Results: 20 of the 97 patients (20.62%) were negative expression of Napsin A （Napsin A-）and 60 (61.86%) were M-CTC positive（M-CTC+). Both Napsin A expression (P=0.004) and M-CTC+ (P<0.001) showed significant correlation to lymphatic metastasis, and M-CTC+ was also significantly correlated with the tumor stage (P=0.009) but was not correlated with gender, age, smoking, tumor size and degree of differentiation. Furthermore, the Napsin A- patients had a higher positive rate of M-CTC. In addition, the recurrence-free survival (RFS; Log-rank P <0.001) and overall survival (OS; Log-rank P <0.001) of the M-CTC+ LUAD patients were significantly worse. Likewise, Napsin A- was also associated with poor RFS (Log-rank P <0.001) and OS (Log-rank P = 0.0003).Conclusion: LUAD patients with Napsin A- have a higher frequency of M-CTC+, and the Napsin A- and M-CTC+ status portends poor prognosis.

Abstract 1737: ALK rearrangement analysis in circulating tumor cells of lung cancer patients

2017 ◽  
Author(s):  
Min Kyung Jeon ◽  
Young Hun Kim ◽  
Eunjoo Hwang ◽  
Hye Seon Lee ◽  
Ji-hyun Uh ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Alk Rearrangement ◽  
Lung Cancer Patients

Comparison of PD-L1 expression between tumor tissues and circulating tumor cells in patients with lung cancer

2016 ◽  
Vol 69 ◽  
pp. S14 ◽  
Author(s):  
Y. Koh ◽  
S. Yagi ◽  
H. Akamatsu ◽  
A. Tanaka ◽  
K. Kanai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Tumor Tissues
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