scholarly journals Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement,ALKsignal copy number, and response to crizotinib therapy inALKfluorescence in situ hybridization-positive nonsmall cell lung cancer

Cancer ◽  
2012 ◽  
Vol 118 (18) ◽  
pp. 4486-4494 ◽  
Author(s):  
D. Ross Camidge ◽  
Mariana Theodoro ◽  
DeLee A. Maxson ◽  
Margaret Skokan ◽  
Tara O'Brien ◽  
...  
Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1465 ◽  
Author(s):  
Arutha Kulasinghe ◽  
Yenkai Lim ◽  
Joanna Kapeleris ◽  
Majid Warkiani ◽  
Ken O’Byrne ◽  
...  

Tumor tissue biopsy is often limited for non-small cell lung cancer (NSCLC) patients and alternative sources of tumoral information are desirable to determine molecular alterations such as anaplastic lymphoma kinase (ALK) rearrangements. Circulating tumor cells (CTCs) are an appealing component of liquid biopsies, which can be sampled serially over the course of treatment. In this study, we enrolled a cohort of ALK-positive (n = 8) and ALK-negative (n = 12) NSCLC patients, enriched for CTCs using spiral microfluidic technology and performed DNA fluorescent in situ hybridization (FISH) for ALK. CTCs were identified in 12/20 NSCLC patients ranging from 1 to 26 CTCs/7.5 mL blood. Our study revealed that 3D imaging of CTCs for ALK translocations captured a well-defined separation of 3′ and 5′ signals indicative of ALK translocations and overlapping 3′/5′ signal was easily resolved by imaging through the nuclear volume. This study provides proof-of-principle for the use of 3D DNA FISH in the determination of CTC ALK translocations in NSCLC.


2020 ◽  
Vol 9 (02) ◽  
pp. 109-114
Author(s):  
Manish Kumar ◽  
Kishore Kumar ◽  
Harinder Pal Singh ◽  
Suresh Nair ◽  
Amol Patel ◽  
...  

Abstract Aims This study aims to evaluate the incidence of anaplastic lymphoma kinase (ALK) mutation in nonsmall cell lung cancer (NSCLC) incorporating fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) methods and to look for any discordance. Methods We evaluated 101 samples obtained from an enriched cohort of NSCLCs patients from the Army Hospital Research and Referral, New Delhi, India, between November 2016 and November 2018. IHC was performed using the highly-sensitive D5F3 rabbit monoclonal primary antibody. FISH was performed with dual-color, break-apart probe (ZytoLight SPEC) on formalin-fixed, and paraffin-embedded tissue. Discordance between IHC and FISH for ALK rearrangements was evaluated. Pearson correlation coefficient (r) was performed to identify any association of ALK presence (by IHC and FISH) with smoking brain metastasis, programmed death-ligand (PD-L1) expression, pleural effusion, and histopathological subtype. Results A total of 7.92% (8/101) cases tested by IHC and 9.9% (10/101) cases tested by FISH were positive for ALK rearrangement. Of 93 ALK IHC-negative cases, 4 were ALK FISH-positive, whereas of 91 ALK FISH-negative cases, 4 were ALK IHC-positive cases. The correlation analysis demonstrated no or very weak correlation in ALK mutations by IHC or FISH with smoking, brain metastasis, PD-L1 expression, pleural effusion, and histopathological examination, except a weak positive correlation (r = 0.33) observed between brain metastasis and ALK rearrangement identified by FISH. Conclusions Our study demonstrated a somewhat similar incidence of ALK FISH-positive cases and ALK IHC-positive cases, though the incidence was numerically higher for ALK-FISH method.


2017 ◽  
Vol 54 (1) ◽  
pp. 203 ◽  
Author(s):  
AP Dubey ◽  
N Pathi ◽  
S Viswanath ◽  
A Rathore ◽  
A Pathak ◽  
...  

2018 ◽  
Vol 7 (1) ◽  
pp. 22
Author(s):  
Mohanad Ali AlBayyaa ◽  
Ban A. Abdulmajeed

Background/Aim: Anaplastic Lymphoma Kinase (ALK) rearrangement has evaluated activity of NSCLC compared with other molecular subtypes (EGFR, KRAS). Many studies demonstrated that patients with ALK rearrangement positive NSCLC have improved with a good response rates and progression (free survival) when treated with either monotherapy or by a combination therapy compared with EGFR-mutated, KRAS/EGFR/ALK wild type or KRAS-mutated. The aim of this study was to detect and study the signal pattern of normal ALK and compare it to that of mutated ALK with gene rearrangement in cases of non-small cell lung cancer and Inflammatory conditions by implementing the CISH technique. In addition to correlate ALK signal pattern with the histopathological type and grade as well as the age and sex of the patients.Materials & Methods: Forty patients with NSCLC and Inflammatory diseases were enrolled in a comparative cross sectional study. The tissue blocks were sectioned on non-charged slides for the preparation of routine H&E staining. Positively charged slides were used for tissue sections prepared for chromogenic in situ hybridization procedure to detect ALK gene.Results: ALK gene signal break apart was detected in (18/20, 90%) of malignant cases; (0/20, 0%) of non-neoplastic lung lesions. There was a significant statistical difference in their distribution, p < 0.05. While There was no significant association between any disease status and sex P value = 1.000NS. The CISH test was 100% sensitive using negative score as a cutoff point and 90.9% specific. The score was divided into three levels that categorized the cases, so there were six cases in score one (1-32%), nine cases in score two (33-67%) and three cases in score three (68-100%).Conclusion: Detection of ALK rearrangement in the early diagnosis of NSCLC is highly sensitive and can save a lot of efforts in planning chemotherapy regimens. Results were very promising in identifying this mutation by a sensitive and highly specific test. The ALK gene rearrangement could be an early mutation and it is needed as an initiating step for the carcinogenesis process. The presence of a double gene mutation, however, could be the cause of a higher-grade cancer.


Lung Cancer ◽  
2013 ◽  
Vol 81 (2) ◽  
pp. 200-206 ◽  
Author(s):  
Maximilian v. Laffert ◽  
Arne Warth ◽  
Roland Penzel ◽  
Peter Schirmacher ◽  
Danny Jonigk ◽  
...  

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