ALK Status Testing in Non–Small-Cell Lung Carcinoma by FISH on ThinPrep Slides with Cytology Material

Minca, Eugen C.; Lanigan, Christopher; Reynolds, Jordan; Wang, Zhen; Patrick, C.; Cicenia, Joseph; Almeida, Francisco A.; Pennell, Nathan A.; Tubbs, Raymond R.

doi:10.1097/jto.0000000000000104

Cited by 54 publications

(58 citation statements)

References 27 publications

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“…assessment of the entire cell nucleus) can be envisioned for performing ALK-FISH directly on ThinPrep slides compared to slides derived from FFPE cell blocks [23]. A large NSCLC cohort with liquid-based cytology material (mainly TBNA specimens) available for ALK status testing demonstrated that the routine use of ThinPrep-FISH is feasible and can reliably detect ALK gene rearrangements [23]. …”

Section: Discussionmentioning

confidence: 99%

Suitability of Small Bronchoscopic Tumour Specimens for Lung Cancer Genotyping

Dooms

Vliegen²,

Borght³

et al. 2014

Respiration

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Background: Biomarker-driven clinical trials in advanced non-small cell lung cancer (NSCLC) usually accept biopsy specimens only, as cytology specimens are supposed to be more challenging due to low neoplastic cell content and suboptimal DNA quantity. Objectives: We aimed to evaluate 2 aspects of bronchoscopic biopsy and cytology specimens: (1) the proportion of neoplastic cells and quantity of DNA extracted, and (2) the detection limit of the Scorpion amplification refractory mutation system on endoscopic samples obtained in daily clinical practice. Methods: We screened 679 patients with advanced-stage NSCLC for the presence of an activating EGFR mutation according to the guidelines of the European Society of Medical Oncology. Their diagnostic tumour tissue samples were characterized. A dilution experiment was performed to determine the minimal proportion of neoplastic cells for a reliable test result. Results: Surgical biopsies, bronchoscopic forceps biopsy samples and needle aspiration cytology specimens exhibited a median tumour cell proportion of 70 versus 30 versus 20% and a DNA quantity of 2,500 versus 1,610 versus 1,440 ng, respectively. The overall EGFR mutation rate was 11%, with no differences between different sample types. Dilution experiments showed that the detection limit depends on the type of mutation. A neoplastic cell content of at least 10 and 25% for exon 19 deletions and exon 21 L858R point mutation, respectively, was required for a true negative result. Conclusions: Bronchoscopic forceps biopsy and needle aspiration cytology specimens are suitable for accurate EGFR mutation analysis using single-gene quantitative real-time polymerase chain reaction. Technologies with a better analytical sensitivity are evolving and should consider these endoscopic tumour specimens.

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Section: Discussionmentioning

confidence: 99%

Suitability of Small Bronchoscopic Tumour Specimens for Lung Cancer Genotyping

Dooms

Vliegen²,

Borght³

et al. 2014

Respiration

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“…Only 2 of the 230 cases (0.8%) tested showed no FISH signals, because of low specimen quantity/quality. 13 In a subset of 154 cases with paired ThinPrep slides and adequately cellular cell blocks, ALK FISH performed on ThinPrep slides had a concordance of 98.7% compared with immunohistochemistry using the ultrasensitive ALK (D5F3) antibody (Ventana Medical Systems, Tucson, Arizona) performed on the corresponding cell block sections. 13 In some cases, the ThinPrep slide has insufficient cellularity for ALK FISH testing.…”

Section: Egfr Mutation Analysismentioning

confidence: 99%

“…13 In a subset of 154 cases with paired ThinPrep slides and adequately cellular cell blocks, ALK FISH performed on ThinPrep slides had a concordance of 98.7% compared with immunohistochemistry using the ultrasensitive ALK (D5F3) antibody (Ventana Medical Systems, Tucson, Arizona) performed on the corresponding cell block sections. 13 In some cases, the ThinPrep slide has insufficient cellularity for ALK FISH testing. In such cases, we perform immunohistochemistry using the ultrasensitive ALK (D5F3) antibody either on the cell block material or on an available surgical pathology specimen.…”

Section: Egfr Mutation Analysismentioning

confidence: 99%

“…An alternate strategy for EGFR and ALK testing was therefore developed, using material from the liquid-based cytology sample for EGFR mutation testing by nextgeneration sequencing (NGS), and the ThinPrep slide for fluorescence in situ hybridization (FISH) testing for ALK gene rearrangements. 12,13 We briefly describe our experience with molecular testing of non-small cell lung carcinomas for EGFR mutations and ALK gene rearrangements on liquidbased cytopathology specimens at our institution, with an emphasis on material obtained from endobronchial ultrasound-guided transbronchial fine-needle aspiration (EBUS-TBNA) procedures.…”

mentioning

confidence: 99%

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Molecular Testing of Non–Small Cell Lung Carcinoma Diagnosed by Endobronchial Ultrasound–Guided Transbronchial Fine-Needle Aspiration: The Cleveland Clinic Experience

Doxtader

Cheng

Zhang

2018

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Given the increasing demand for molecular testing of non–small cell lung carcinoma specimens to guide therapeutic decision-making and the trend toward minimally invasive techniques for obtaining diagnostic tissue, cytopathology laboratories must devise strategies to maximize DNA yield for necessary molecular testing. Objective.— To describe our experience at Cleveland Clinic with epidermal growth factor receptor (EGFR) mutation testing by next-generation sequencing and anaplastic lymphoma kinase (ALK) gene rearrangement testing by fluorescence in situ hybridization of non–small cell lung carcinomas diagnosed by cytology, with an emphasis on specimens obtained by endobronchial ultrasound–guided transbronchial fine-needle aspiration. Data Sources.— Data sources include a review of the current literature, including published articles from our institution. Conclusions.— At our institution, liquid-based cytology specimens are the primary resource used for molecular testing of non–small cell lung carcinomas; in most instances, adequate DNA can be extracted from the residual cell pellet for next-generation sequencing, and ThinPrep slides can be used reliably for fluorescence in situ hybridization testing for ALK gene rearrangements. In occasional cases where the cell pellet material is not adequate for molecular testing, cell blocks and/or surgical pathology specimens are secondary options. The cytopathologist's role in specimen handling and triage is essential to ensure that molecular testing can be carried out successfully.

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“…The same efficacy has been reported in lung cancer cytopathology. FISH has been shown to be a reliable method for the detection of ALK rearrangements in LBC [71] in endobranchial ultrasound-guided transbronchial needle aspiration [72] or direct smears [73]. …”

Section: Quality Control In Cytopathologymentioning

confidence: 99%

Is Liquid-Based Cytology the Magic Bullet for Performing Molecular Techniques?

Abedi-Ardekani

Vielh²

2014

Acta Cytologica

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Objective: The role of pathology has evolved from the first microscopic definitions of diseases by Virchow to the new concept of molecular cytopathology. The management of diseases is now a multidisciplinary approach with the translation of morphological, imagery and molecular findings to therapeutic protocols. Obtaining the most reliable diagnostic material is the essential part of the medical management of patients. Study Design: Here, we try to gain a concise insight into the available data regarding the role of cytology in the application of molecular techniques, focusing on cancer cytopathology. Results: Obtaining cytological material is now feasible by different methods, and in some cases it is the only possible approach to a lesion which is not easily accessible for tissue sampling. The methods of obtaining cytological material have evolved in recent years in parallel with rapid advances in high-throughput molecular techniques, opening new windows for the diagnosis and management of diseases. Conclusions: Different kinds of cytological material are reliable for the application of molecular techniques. Cytological material obtained in a liquid base has advantages such as the better preservation of cytomorphological features and the use of the remaining liquid for nucleic acid extraction even after long storage and the application of molecular methods.

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ALK Status Testing in Non–Small-Cell Lung Carcinoma by FISH on ThinPrep Slides with Cytology Material

Abstract: Detection of ALK gene rearrangements in liquid cytology ThinPrep slides derived from patients with NSCLC can be confidently used for clinical ALK molecular testing.

Cited by 54 publications

References 27 publications

Suitability of Small Bronchoscopic Tumour Specimens for Lung Cancer Genotyping

Suitability of Small Bronchoscopic Tumour Specimens for Lung Cancer Genotyping

Molecular Testing of Non–Small Cell Lung Carcinoma Diagnosed by Endobronchial Ultrasound–Guided Transbronchial Fine-Needle Aspiration: The Cleveland Clinic Experience

Is Liquid-Based Cytology the Magic Bullet for Performing Molecular Techniques?

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