<scp>ALK</scp> and ROS1 rearrangements tested by fluorescence in situ hybridization in cytological smears from advanced non‐small cell lung cancer patients

Bozzetti, Cecilia; Nizzoli, Rita; Tiseo, Marcello; Squadrilli, Anna; Lagrasta, Costanza; Buti, Sebastiano; Gasparro, Donatello; Zanoni, Daniele; Majori, Maria; Filippo, Massimo De; Mazzoni, Francesca; Maddau, Cristina; Naldi, Nadia; Sammarelli, Gabriella; Frati, Caterina; Pinto, Carmine; Ardizzoni, Andrea

doi:10.1002/dc.23318

Cited by 35 publications

(35 citation statements)

References 31 publications

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“…In the present tumor, we found signet‐ring cell morphology in cytological specimens. These findings were not observed in the previously reported cytological specimens . Furthermore, we confirmed the positivity for ROS1 immunohistochemistry (IHC) using cell‐transferred method .…”

Section: Discussionsupporting

confidence: 84%

“…Lung adenocarcinoma with ROS1 ‐rearrangement has been recently identified . Although microscopic features of ROS1 ‐rearranged lung adenocarcinoma have been described in several reports, there is only one report in cytological findings . The role of cytology is very important in the workup of pulmonary lesions and it is crucial to establish molecular testing on cytological specimens.…”

Section: Introductionmentioning

confidence: 99%

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Cytological findings of ROS1‐rearranged lung adenocarcinoma

Tamiya

Nakatani

Wada

et al. 2017

Diagnostic Cytopathology

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ROS1-rearranged lung adenocarcinoma has been recently identified. We report a case of ROS1-rearranged lung adenocarcinoma with special emphasis on cytological findings. Here, we report a case of young woman with ROS1-rearranged lung adenocarcinoma diagnosed by cytology and discuss the clinical, cytological, and molecular findings. Cytologically, the tumor consisted of small tight clusters of cells with high nuclear/cytoplasmic ratio. Nuclei were enlarged and small nucleoli were occasionally observed. Signet-ring cells were focally identified. Neoplastic cells were positive for ROS1 immunocytochemistry. Subsequently, the translocation of ROS1 gene was confirmed in a histological specimen. In conclusion, the specific histology of adenocarcinoma on cytological materials should promote testing for ROS1 immunohistochemistry. Immunocytochemical detection of ROS1 protein helps identify patients suitable for molecular targeted therapy.

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Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Cytological findings of ROS1‐rearranged lung adenocarcinoma

Tamiya

Nakatani

Wada

et al. 2017

Diagnostic Cytopathology

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“…BioView Duet system, Rehovot, Israel) can facilitate FISH scoring. It should be noted that FISH testing for ROS1 (and ALK ) is not restricted to histological tissue sections, but is also applicable to cytological specimens [39, 40]. …”

Section: Detection Of Ros1 Gene Rearrangementsmentioning

confidence: 99%

Testing for ROS1 in non-small cell lung cancer: a review with recommendations

et al. 2016

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Rearrangements of the ROS1 gene occur in 1–2 % of non-small cell lung cancers (NSCLCs). Crizotinib, a highly effective inhibitor of ROS1 kinase activity, is now FDA-approved for the treatment of patients with advanced ROS1-positive NSCLC. Consequently, focus on ROS1 testing is growing. Most laboratories currently rely on fluorescence in situ hybridisation (FISH) assays using a dual-colour break-apart probe to detect ROS1 rearrangements. Given the rarity of these rearrangements in NSCLC, detection of elevated ROS1 protein levels by immunohistochemistry may provide cost-effective screening prior to confirmatory FISH testing. Non-in situ testing approaches also hold potential as stand-alone methods or complementary tests, including multiplex real-time PCR assays and next-generation sequencing (NGS) platforms which include commercial test kits covering a range of fusion genes. In order to ensure high-quality biomarker testing, appropriate tissue handling, adequate control materials and participation in external quality assessment programmes are essential, irrespective of the testing technique employed. ROS1 testing is often only considered after negative tests for EGFR mutation and ALK gene rearrangement, based on the assumption that these oncogenic driver events tend to be exclusive. However, as the use of ROS1 inhibitors becomes routine, accurate and timely detection of ROS1 gene rearrangements will be critical for the optimal treatment of patients with NSCLC. As NGS techniques are introduced into routine diagnostic practice, ROS1 fusion gene testing will be provided as part of the initial testing package.

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“…19 The green fluorochrome is the part containing the kinase domain of ROS1 gene. FISH testing for ROS1 is applicable either on biopsy or in cytologic specimens, and the cut-off of rearranged signals to quote ROS1 positivity is based on detection of 15% or more among 50 neoplastic nuclei 66,67…”

Section: Introductionmentioning

confidence: 99%

Detection of ROS1 rearrangement in non-small cell lung cancer: current and future perspectives

Rossi¹,

Jocollè

Conti³

et al. 2017

LCTT

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ROS1 rearrangement characterizes a small subset (1%–2%) of non-small cell lung cancer and is associated with slight/never smoking patients and adenocarcinoma histology. Identification of ROS1 rearrangement is mandatory to permit targeted therapy with specific inhibitors, demonstrating a significantly better survival when compared with conventional chemotherapy. Detection of ROS1 rearrangement is based on in situ (immunohistochemistry, fluorescence in situ hybridization) and extractive non-in situ assays. While fluorescence in situ hybridization still represents the gold standard in clinical trials, this technique may fail to recognize rearrangements of ROS1 with some gene fusion partner. On the other hand, immunohistochemistry is the most cost-effective screening technique, but it seems to be characterized by low specificity. Extractive molecular assays are expensive and laborious methods, but they specifically recognize almost all ROS1 fusions using a limited amount of mRNA even from formalin-fixed, paraffin-embedded tumor tissues. This review is a discussion on the present and futuristic diagnostic scenario of ROS1 identification in lung cancer.

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ALK and ROS1 rearrangements tested by fluorescence in situ hybridization in cytological smears from advanced non‐small cell lung cancer patients

Abstract: Whenever cytology represents the only available material for diagnosis and biological characterization of NSCLC, minimally invasive procedures may provide an additional important source of cellular material for FISH assessment of ALK and ROS1 rearrangements.

Cited by 35 publications

References 31 publications

Cytological findings of ROS1‐rearranged lung adenocarcinoma

Cytological findings of ROS1‐rearranged lung adenocarcinoma

Testing for ROS1 in non-small cell lung cancer: a review with recommendations

Detection of ROS1 rearrangement in non-small cell lung cancer: current and future perspectives

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