Dichotomous ALK-IHC Is a Better Predictor for ALK Inhibition Outcome than Traditional ALK-FISH in Advanced Non–Small Cell Lung Cancer

Wekken, Anthonie J. van der; Pelgrim, R.; Hart, Nils ’t; Werner, Naomi; Mastik, Mirjam F.; Hendriks, Lizza; Heijden, Erik H F M van der; Looijen-Salamon, Monika; Langen, Adrianus J. de; Brekel, J. Staal-van den; Riemersma, Sietske A.; Borne, B.E. van den; Speel, Ernst J. M.; Dingemans, Anne Marie C.; Hiltermann, T Jeroen N; Berg, Anke van den; Timens, Wim; Schuuring, Ed; Groen, Harry J.M.

doi:10.1158/1078-0432.ccr-16-1631

Cited by 63 publications

(50 citation statements)

References 31 publications

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“…Although ALK was substantially expressed in this case, no gene rearrangement or amplification was detected. An increasing number of studies have shown that ALK IHCpositive and FISH-negative tumors may still respond to crizotinib [13,23]. Together, these data suggest that ALK inhibitors may be a potential therapeutic option for ALKpositive p.D842V mutation-harboring GIST.…”

Section: Discussionmentioning

confidence: 92%

ALK expressed in a gastrointestinal stromal tumor harboring PDGFRA p. D842V mutation:a case report

et al. 2020

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Background: Gastrointestinal stromal tumors (GISTs) are the most common type of adult mesenchymal neoplasms.The events that drive GIST oncogenesis are primarily KIT or PDGFRA mutations, which lead to the susceptibility of these tumors to small-molecule tyrosine kinase inhibitors such as imatinib and sunitinib. However, previous studies have shown that patients with a PDGFRA D842V mutation in GISTs have a very low rate of response to imatinib treatment. Therefore, novel tyrosine kinase inhibitors (TKIs) are currently being evaluated in clinical trials to treat GISTs harboring a PDGFRA D842V mutation. Anaplastic lymphoma kinase (ALK) overexpression was not expected to be present in the GIST, and it has been used as a biomarker to distinguish GISTs from other types of mesenchymal tumors. Case presentation: Here, we report a 37-year-old male patient who presented with a large mass in the right upper abdomen and was subsequently diagnosed with a GIST harboring a PDGFRA D842V mutation. We unexpectedly found that the GIST in this patient exhibited simultaneous ALK expression. Conclusions: This is the first case reported of a GIST with ALK expression. This rare phenomenon suggests that the diagnosis of a GIST cannot be excluded absolutely if a tumor exhibits ALK expression. In addition, ALK may be a potential therapeutic target for patients with imatinib-resistant stromal tumors.

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Section: Discussionmentioning

confidence: 92%

ALK expressed in a gastrointestinal stromal tumor harboring PDGFRA p. D842V mutation:a case report

et al. 2020

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“…Several other studies have also reported the possibility of false results from FISH assays and have strongly suggested that NGS be used to resolve IHC-FISH discordant cases [20][21][22][23][24]. In addition, the re-validation of molecular testing would be useful in the treatment of tumors that are unresponsive to target agents.…”

Section: Discussionmentioning

confidence: 99%

Detection of Targetable Genetic Alterations in Korean Lung Cancer Patients: A Comparison Study of Single-Gene Assays and Targeted Next-Generation Sequencing

Park

Shim

2020

Cancer Res Treat

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PurposeEpidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1 (ROS1) are ‘must-test’ biomarkers in the molecular diagnostics of advanced-stage lung cancer patients. Although single-gene assays are currently considered the gold standard for these genes, next-generation sequencing (NGS) tests are being introduced to clinical practices. We compared the results of current diagnostics and aimed to suggest timely effective guidance for their clinical use. Materials and MethodsPatients with lung cancer who received both conventional single-gene assays and subsequent targeted NGS testing were enrolled, and the results of their tests were compared. ResultsA total of 241 patients were enrolled, and the EGFR real-time polymerase chain reaction, ALK fluorescence in situ hybridization (FISH), and ROS1 FISH assays exhibited 92.9%, 99.6%, and 99.5% concordance with the NGS tests, respectively. The discordant cases were mostly false-negatives of the single-gene assays, probably due to technical limitation. Of 158 cases previously designated as wild-type, EGFR, ALK, and ROS1 alterations were identified in 10.1%, 1.9%, and 1.3%, respectively, and other targetable alterations were identified in 36.1% of the cases. Of patients with additionally identified actionable alterations, 32.6% (31/95) received matched therapy with a clinical benefit of 48.4% (15/31). ConclusionEven though the conventional and NGS methods were concordant in the majority of cases, NGS testing still revealed a considerable number of additional EGFR, ALK, and ROS1 alterations, as well as other targetable alterations, in Korean advanced-stage lung cancer patients. Given the high frequency of EGFR and other targetable mutations identified in the present study, NGS testing is highly recommended in the diagnosis of Korean lung cancer patients.

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“…The FDA have approved tyrosine kinase ALK inhibitors, crizotinib, alectinib and ceritinib. Crizotinib, registered in 2010, was the first drug for ALK positive fusion treatment [27][28][29] .…”

Section: Clinical Biomarkers Currently Used In Therapeutic Strategiesmentioning

confidence: 99%

“…NGS is technology with the ability to perform and capture data from millions of sequencing reactions simultaneously. All NGS platforms are able to catch the individual sequence of hundreds of millions of molecules at the genome or transcriptome level 28,[64][65][66][67] . One obstacle to initiating NGS in routine practice is the high initial costs as it method is currently more expensive than the methods above.…”

Section: Gene Rearrangement Detection In Nsclc Patientsmentioning

confidence: 99%

Gene rearrangement detection by next-generation sequencing in patients with non-small cell lung carcinoma

Brisudova¹,

Škarda²

2020

BIOMED PAP

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Non-small cell lung carcinoma (NSCLC) is the leading cause of cancer-related deaths worldwide. Various molecular markers in NSCLC patients have been developed, including gene rearrangements, currently used in therapeutic strategies. With increasing number of these molecular biomarkers of NSCLC, there is a demand for highly efficient methods for detecting mutations and translocations in treatable targets. Those currently available U.S. Food and Drug Administration (FDA) approved approaches, for example imunohistochemisty (IHC) and fluorescence in situ hybridization (FISH), are inadequate, due to sufficient quantity of material and long time duration. Next-generation massive parallel sequencing (NGS), with the ability to perform and capture data from millions of sequencing reactions simultaneously could resolve the problem. Thanks to gradual NGS introduction into clinical laboratories, screening time should be considerably shorter, which is very important for patients with advanced NSCLC. Moreover, only a minimum sample input is needed for achieving adequate results. NGS was compared to the current detection methods of ALK, ROS1, c-RET and c-MET rearrangements in NSCLC and a significant match, between IHC, FISH and NGS results, was found. Recent available researches have been carried out on a small numbers of patients. Verifying these results on larger patients cohort is important. This review sumarizes the literature on this subject and compares current possibilities of predictive gene rearrangements detection in patients with NSCLC.

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Dichotomous ALK-IHC Is a Better Predictor for ALK Inhibition Outcome than Traditional ALK-FISH in Advanced Non–Small Cell Lung Cancer

Cited by 63 publications

References 31 publications

ALK expressed in a gastrointestinal stromal tumor harboring PDGFRA p. D842V mutation:a case report

ALK expressed in a gastrointestinal stromal tumor harboring PDGFRA p. D842V mutation:a case report

Detection of Targetable Genetic Alterations in Korean Lung Cancer Patients: A Comparison Study of Single-Gene Assays and Targeted Next-Generation Sequencing

Gene rearrangement detection by next-generation sequencing in patients with non-small cell lung carcinoma

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