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Comparison of ROS1-...
Comparison of ROS1-rearrangement detection methods in a cohort of surgically resected non-small cell lung carcinomas
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- Thurfjell, Viktoria (author)
- Uppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Micke, Patrick (author)
- Uppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Yu, Hui (author)
- Uppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Krupar, Rosemarie (author)
- Division of Pathology, Research Center Borstel, Leibniz Lung Center, Borstel, Germany; Institute of Pathology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany,University Medical Center Schleswig-Holstein,Forschungszentrum Borstel - Zentrum für Medizin und Biowissenschaften
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- Svensson, Maria A., 1980- (author)
- Örebro University,Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län,Clinical Research Center
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- Brunnström, Hans (author)
- Lund University,Lunds universitet,Division of Pathology, Lund University and Laboratory Medicine Region Skåne, Lund, Sweden,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Patologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Pathology, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Lamberg, Kristina (author)
- Uppsala universitet,Lung- allergi- och sömnforskning,Uppsala University Hospital
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- Moens, Lotte (author)
- Uppsala University,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory (SciLifeLab)
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- Strell, Carina (author)
- Uppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Gulyas, Miklos, MD, PhD, Associate Professor, 1959- (author)
- Uppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Helenius, Gisela, 1973- (author)
- Örebro universitet,Institutionen för medicinska vetenskaper,Department of Laboratory Medicine
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- Yoshida, Akihiko (author)
- Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan
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- Goldmann, Torsten (author)
- Division of Pathology, Research Center Borstel, Leibniz Lung Center, Borstel, Germany; Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Großhansdorf, Germany,Forschungszentrum Borstel - Zentrum für Medizin und Biowissenschaften
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- Mattsson, Johanna Sofia Margareta, 1985- (author)
- Uppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi
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(creator_code:org_t)
- 2022-12
- 2022
- English.
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In: Translational Lung Cancer Research (TLCR). - : AME Publishing. - 2218-6751 .- 2226-4477. ; 11:12, s. 2477-2494
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Abstract
Subject headings
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- 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=40 1, squamous cell carcinomas (SCC) n=2 13, other NSCLC n=62]. ROS1rearrangements 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
Keyword
- Crizotinib
- ROS proto-oncogene 1 (ROS1)
- fusion gene detection
- molecular pathology
- targeted therapy
- Crizotinib
- fusion gene detection
- molecular pathology
- ROS proto-oncogene 1 (ROS1)
- targeted therapy
Publication and Content Type
- ref (subject category)
- art (subject category)
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Thurfjell, Vikto ...
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Micke, Patrick
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Yu, Hui
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Krupar, Rosemari ...
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Svensson, Maria ...
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Brunnström, Hans
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Lamberg, Kristin ...
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Moens, Lotte
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Strell, Carina
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Gulyas, Miklos, ...
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Helenius, Gisela ...
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Yoshida, Akihiko
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Goldmann, Torste ...
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Mattsson, Johann ...
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Örebro University
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Uppsala University
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Lund University