Evidence map›Paper›PMID 36636421›Full record

ArticleTranslational lung cancer research2022

Comparison of ROS1-rearrangement detection methods in a cohort of surgically resected non-small cell lung carcinomas.

Viktoria Thurfjell, Patrick Micke, Hui Yu, Rosemarie Krupar, Maria A Svensson, Hans Brunnström, Kristina Lamberg, Lotte N J Moens, Carina Strell, Miklos Gulyas and 4 more

Abstract read
In one paragraph

Article in Translational lung cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Viktoria Thurfjell *Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Patrick Micke *Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Hui YuDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Rosemarie KruparDivision of Pathology, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
Maria A SvenssonClinical Research Center, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
Hans BrunnströmDivision of Pathology, Lund University and Laboratory Medicine Region Skåne, Lund, Sweden.
Kristina LambergDepartment of Pulmonary and Allergic Diseases, Uppsala University Hospital, Uppsala, Sweden.
Lotte N J MoensDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Carina StrellDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Miklos GulyasDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Gisela HeleniusDepartment of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
Akihiko YoshidaDepartment of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan.
Torsten Goldmann *Division of Pathology, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
Johanna Sofia Margareta Mattsson *Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Patients with non-small cell lung cancer (NSCLC) harboring a ROS proto-oncogene 1 (ROS1)-rearrangement respond to treatment with ROS1 inhibitors. To distinguish these rare cases, screening with immunohistochemistry (IHC) for ROS1 protein expression has been suggested. However, the reliability of such an assay and the comparability of the antibody clones has been debated. Therefore we evaluated the diagnostic performance of current detection strategies for ROS1-rearrangement in two NSCLC-patient cohorts. Methods: Resected tissue samples, retrospectively collected from consecutive NSCLC-patients surgically treated at Uppsala University Hospital were incorporated into tissue microarrays [all n=676, adenocarcinomas (AC) n=401, squamous cell carcinomas (SCC) n=213, other NSCLC n=62]. ROS1-rearrangements were detected using fluorescence in situ hybridization (FISH) (Abbott Molecular; ZytoVision). In parallel, ROS1 protein expression was detected using IHC with three antibody clones (D4D6, SP384, EPMGHR2) and accuracy, sensitivity, and specificity were determined. Gene expression microarray data (Affymetrix) and RNA-sequencing data were available for a subset of patients. NanoString analyses were performed for samples with positive or ambiguous results (n=21). Results: Using FISH, 2/630 (0.3% all NSCLC; 0.5% non-squamous NSCLC) cases were positive for ROS1 fusion. Additionally, nine cases demonstrated ambiguous FISH results. Using IHC, ROS1 protein expression was detected in 24/665 (3.6% all NSCLC; 5.1% non-squamous NSCLC) cases with clone D4D6, in 18/639 (2.8% all NSCLC; 3.9% non-squamous NSCLC) cases with clone SP384, and in 1/593 (0.2% all NSCLC; 0.3% non-squamous NSCLC) case with clone EPMGHR2. Elevated RNA-levels were seen in 19/369 (5.1%) cases (Affymetrix and RNA-sequencing combined). The overlap of positive results between the assays was poor. Only one of the FISH-positive cases was positive with all antibodies and demonstrated high RNA-expression. This rearrangement was confirmed in the NanoString-assay and also in the RNA-sequencing data. Other cases with high protein/RNA-expression or ambiguous FISH were negative in the NanoString-assay. Conclusions: The occurrence of ROS1 fusions is low in our cohorts. The IHC assays detected the fusions, but the accuracy varied depending on the clone. The presumably false-positive and uncertain FISH results questions this method for detection of ROS1-rearrangements. Thus, when IHC is used for screening, transcript-based assays are preferable for validation in clinical diagnostics.

Indexed as

Crizotinibfusion gene detectionmolecular pathologyROS proto-oncogene 1 (ROS1)targeted therapy

Identifiers

PMID36636421
PMCPMC9830269

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.