Fluorescence In Situ Hybridization, Immunohistochemistry, and Next-Generation Sequencing for Detection of EML4-ALK Rearrangement in Lung Cancer

Pekar-Zlotin, Marina; Hirsch, Fred R.; Soussan‐Gutman, Lior; Ilouze, Maya; Dvir, Addie; Boyle, Theresa A.; Wynes, Murry W.; Miller, Vincent A.; Lipson, Doron; Palmer, Gary A.; Ali, Siraj M.; Shlomi, Dekel; Brenner, Ronen; Bunn, Paul A.; Peled, Nir

doi:10.1634/theoncologist.2014-0389

Cited by 143 publications

(143 citation statements)

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“…There is a consistent body of evidence demonstrating that IHC is comparable, if not superior, to FISH (44,45). In a recent study (46), the sensitivity and specificity were 43% and 98% for FISH and 100% and 98% for IHC, respectively. Relevant discrepancies between FISH and IHC results have indeed been reported (47)(48)(49).…”

Section: Ihcmentioning

confidence: 97%

Tackling ALK in non-small cell lung cancer: the role of novel inhibitors

Facchinetti¹,

Tiseo²,

Maïo³

et al. 2016

Transl. Lung Cancer Res.

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Abstract:Crizotinib is an oral inhibitor of anaplastic lymphoma kinase (ALK) with remarkable clinical activity in patients suffering from ALK-rearranged non-small cell lung cancer (NSCLC), accounting to its superiority compared to chemotherapy. Unfortunately, virtually all ALK-rearranged tumors acquire resistance to crizotinib, frequently within one year since the treatment initiation. To date, therapeutic strategies to overcome crizotinib resistance have focused on the use of more potent and structurally different compounds. Second-generation ALK inhibitors such as ceritinib (LDK378), alectinib (CH5424802/ RO5424802) and brigatinib (AP26113) have shown relevant clinical activity, consequently fostering their rapid clinical development and their approval by health agencies. The third-generation inhibitor lorlatinib (PF-06463922), selectively active against ALK and ROS1, harbors impressive biological potency; its efficacy in reversing resistance to crizotinib and to other ALK inhibitors is being proven by early clinical trials. The NTRK1-3 and ROS1 inhibitor entrectinib (RXDX-101) has been reported to act against NSCLC harboring ALK fusion proteins too. Despite the quick development of these novel agents, several issues remain to be discussed in the treatment of patients suffering from ALK-rearranged NSCLC. This position paper will discuss the development, the current evidence and approvals, as long as the future perspectives of new ALK inhibitors beyond crizotinib. Clinical behaviors of ALK-rearranged NSCLC vary significantly among patients and differential molecular events responsible of crizotinib resistance account for the most important quote of this heterogeneity. The precious availability of a wide range of active anti-ALK compounds should be approached in a critical and careful perspective, in order to develop treatment strategies tailored on the disease evolution of every single patient.

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Section: Ihcmentioning

confidence: 97%

Tackling ALK in non-small cell lung cancer: the role of novel inhibitors

Facchinetti¹,

Tiseo²,

Maïo³

et al. 2016

Transl. Lung Cancer Res.

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show abstract

“…We report here 2 cases in which initial standard of care ALK testing by FISH yielded false positive results, leading to delays in determination of optimal systemic therapy. may occur due to variant forms of EML4-ALK rearrangements and/or RNA editing abnormalities resulting in intron changes that cannot be detected by FISH [4]. Several groups have published on the comparative accuracy of FISH, IHC, and NGS; however, the sensitivity, specificity, and cost of these modalities have not been directly compared in large prospective trials to date [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Fishing for Precision in ALK-Rearranged Non-Small-Cell Lung Cancers

Le¹,

Peters²

2015

Oncology and cancer case reports

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“…I thank Dr. Uguen et al [1] for their comments on the study on the use of fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and next-generation sequencing (NGS) for the detection of EML4-ALK rearrangement in lung cancer [2]. The study under discussion aims to emphasize the obstacles in technology rather than provide incidence of ALK positivity in our cohort.…”

mentioning

confidence: 99%