ROS1 rearrangements in lung adenocarcinomas are defined by diffuse strong immunohistochemical expression of ROS1

Fielder, Timothy; Butler, Jordan; Tierney, Geraldine; Holmes, Mikaela; Lam, K.Y.; Satgunaseelan, Laveniya; Colebatch, Andrew J.; Mahar, Annabelle; Gupta, Ruta; O’Toole, Sandra A.; Cooper, Wendy A.

doi:10.1016/j.pathol.2021.07.012

Cited by 7 publications

(6 citation statements)

References 18 publications

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“…Moreover, it is important to consider which ROS1 antibody is being used since the specificity and sensitivity of these antibodies can be variable [ 21 , 22 , 23 , 24 ]. The determination of an H-score from ROS1 IHC can have added value to set up a cutoff for whether to perform ROS1 FISH to confirm the results [ 25 ]. This was not confirmed in the present study.…”

Section: Discussionmentioning

confidence: 99%

A Real-World Experience from a Single Center (LPCE, Nice, France) Highlights the Urgent Need to Abandon Immunohistochemistry for ROS1 Rearrangement Screening of Advanced Non-Squamous Non-Small Cell Lung Cancer

Hofman

Goffinet

Bontoux

et al. 2023

JPM

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The detection of ROS1 rearrangements in metastatic non-squamous non-small cell lung carcinoma (NS-NSCLC) permits administration of efficient targeted therapy. Detection is based on a testing algorithm associated with ROS1 immunohistochemistry (IHC) screening followed by ROS1 FISH and/or next generation sequencing (NGS) to confirm positivity. However, (i) ROS1 rearrangements are rare (1–2% of NS-NSCLC), (ii) the specificity of ROS1 IHC is not optimal, and (iii) ROS1 FISH is not widely available, making this algorithm challenging to interpret time-consuming. We evaluated RNA NGS, which was used as reflex testing for ROS1 rearrangements in NS-NSCLC with the aim of replacing ROS1 IHC as a screening method. ROS1 IHC and RNA NGS were prospectively performed in 810 NS-NSCLC. Positive results were analyzed by ROS1 FISH. ROS1 IHC was positive in 36/810 (4.4%) cases that showed variable staining intensity while NGS detected ROS1 rearrangements in 16/810 (1.9%) cases. ROS1 FISH was positive in 15/810 (1.8%) of ROS1 IHC positive cases and in all positive ROS1 NGS cases. Obtaining both ROS1 IHC and ROS1 FISH reports took an average of 6 days, while obtaining ROS1 IHC and RNA NGS reports took an average of 3 days. These results showed that systematic screening for the ROS1 status using IHC must be replaced by NGS reflex testing.

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Section: Discussionmentioning

confidence: 99%

A Real-World Experience from a Single Center (LPCE, Nice, France) Highlights the Urgent Need to Abandon Immunohistochemistry for ROS1 Rearrangement Screening of Advanced Non-Squamous Non-Small Cell Lung Cancer

Hofman

Goffinet

Bontoux

et al. 2023

JPM

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“…False-positive outcomes may occur in one-third of patients, especially in those with adhesive or adenomatous EGFR-mutant glandular cancer (Wang et al, 2020;Makarem et al, 2021). Therefore, positive or suspicious IHC results require further confirmation by FISH, reverse -transcription quantitative polymerase chain reaction (RT-qPCR), or next-generation sequencing (NGS) (Hofman et al, 2019;Cheung et al, 2021;Fielder et al, 2022).…”

Section: Methods Of Ros1 Detectionmentioning

confidence: 99%

Progress of non-small-cell lung cancer with ROS1 rearrangement

Yang,

Tang,

et al. 2023

Front. Mol. Biosci.

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ROS1 rearrangement is found in 0.9%–2.6% of people with non-small-cell lung cancers (NSCLCs). Tyrosine kinase inhibitors (TKIs) target ROS1 and can block tumor growth and provide clinical benefits to patients. This review summarizes the current knowledge on ROS1 rearrangements in NSCLCs, including the mechanisms of ROS1 oncogenicity, epidemiology of ROS1-positive tumors, methods for detecting rearrangements, molecular characteristics, therapeutic agents, and mechanisms of drug resistance.

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“…However, FISH is expensive, and the requirements for tissue specimens are stringent, such as tissue sections from infants under 6 months of age 56 . Furthermore, FISH must be detected in more than 50 cell nuclei for diagnostic significance 61 . In addition, some fusion partners of ROS1 (GOPC‐ROS1) cannot be detected by FISH owing to the limitations in the probe design 62 ; self‐designed probes can overcome this limitation 63,64 .…”

Section: Diagnosis Of Ros1 Gene Mutationsmentioning

confidence: 99%

“… 56 Furthermore, FISH must be detected in more than 50 cell nuclei for diagnostic significance. 61 In addition, some fusion partners of ROS1 (GOPC‐ROS1) cannot be detected by FISH owing to the limitations in the probe design 62 ; self‐designed probes can overcome this limitation. 63 , 64 However, FISH remains the gold standard for detecting ROS1 gene mutations.…”

Section: Diagnosis Of Ros1 Gene Mutationsmentioning

confidence: 99%

Current treatment and novel insights regarding ROS1‐targeted therapy in malignant tumors

Li,

Zhang,

Chen

et al. 2024

Cancer Medicine

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BackgroundThe proto‐oncogene ROS1 encodes an intrinsic type I membrane protein of the tyrosine kinase/insulin receptor family. ROS1 facilitates the progression of various malignancies via self‐mutations or rearrangements. Studies on ROS1‐directed tyrosine kinase inhibitors have been conducted, and some have been approved by the FDA for clinical use. However, the adverse effects and mechanisms of resistance associated with ROS1 inhibitors remain unknown. In addition, next‐generation ROS1 inhibitors, which have the advantage of treating central nervous system metastases and alleviating endogenous drug resistance, are still in the clinical trial stage.MethodIn this study, we searched relevant articles reporting the mechanism and clinical application of ROS1 in recent years; systematically reviewed the biological mechanisms, diagnostic methods, and research progress on ROS1 inhibitors; and provided perspectives for the future of ROS1‐targeted therapy.ResultsROS1 is most expressed in malignant tumours. Only a few ROS1 kinase inhibitors are currently approved for use in NSCLC, the efficacy of other TKIs for NSCLC and other malignancies has not been ascertained. There is no effective standard treatment for adverse events or resistance to ROS1‐targeted therapy. Next‐generation TKIs appear capable of overcoming resistance and delaying central nervous system metastasis, but with a greater incidence of adverse effects.ConclusionsFurther research on next‐generation TKIs regarding the localization of ROS1 and its fusion partners, binding sites for targeted drugs, and coadministration with other drugs is required. The correlation between TKIs and chemotherapy or immunotherapy in clinical practice requires further study.

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ROS1 rearrangements in lung adenocarcinomas are defined by diffuse strong immunohistochemical expression of ROS1

Cited by 7 publications

References 18 publications

A Real-World Experience from a Single Center (LPCE, Nice, France) Highlights the Urgent Need to Abandon Immunohistochemistry for ROS1 Rearrangement Screening of Advanced Non-Squamous Non-Small Cell Lung Cancer

A Real-World Experience from a Single Center (LPCE, Nice, France) Highlights the Urgent Need to Abandon Immunohistochemistry for ROS1 Rearrangement Screening of Advanced Non-Squamous Non-Small Cell Lung Cancer

Progress of non-small-cell lung cancer with ROS1 rearrangement

Current treatment and novel insights regarding ROS1‐targeted therapy in malignant tumors

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