PMID- 37237384 OWN - NLM STAT- MEDLINE DCOM- 20230529 LR - 20230530 IS - 1746-1596 (Electronic) IS - 1746-1596 (Linking) VI - 18 IP - 1 DP - 2023 May 27 TI - "Evaluation of ROS1 expression and rearrangements in a large cohort of early-stage lung cancer". PG - 70 LID - 10.1186/s13000-023-01357-1 [doi] LID - 70 AB - BACKGROUND: ROS1 fusion is an infrequent, but attractive target for therapy in patients with metastatic non- small-cell lung cancer. In studies on mainly late-stage disease, the prevalence of ROS1 fusions is about 1-3%. In early-stage lung cancer ROS1 might also provide a fruitful target for neoadjuvant or adjuvant therapy. In the present study, we investigated the prevalence of ROS1 fusion in a Norwegian cohort of early-stage lung cancer. We also explored whether positive ROS1 immunohistochemical (IHC) stain was associated with certain mutations, clinical characteristics and outcomes. METHODS: The study was performed using biobank material from 921 lung cancer patients including 542 patients with adenocarcinoma surgically resected during 2006-2018. Initially, we screened the samples with two different IHC clones (D4D6 and SP384) targeting ROS1. All samples that showed more than weak or focal staining, as well as a subgroup of negative samples, were analyzed with ROS1 fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) with a comprehensive NGS DNA and RNA panel. Positive ROS1-fusion was defined as those samples positive in at least two of the three methods (IHC, FISH, NGS). RESULTS: Fifty cases were IHC positive. Of these, three samples were both NGS and FISH-positive and considered positive for ROS1 fusion. Two more samples were FISH positive only, and whilst IHC and NGS were negative. These were also negative with Reverse Transcription quantitative real time Polymerase Chain Reaction (RT-qPCR). The prevalence of ROS1 fusion in adenocarcinomas was 0.6%. All cases with ROS1 fusion had TP53 mutations. IHC-positivity was associated with adenocarcinoma. Among SP384-IHC positive cases we also found an association with never smoking status. There was no association between positive IHC and overall survival, time to relapse, age, stage, sex or pack-year of smoking. CONCLUSIONS: ROS1 seems to be less frequent in early-stage disease than in advanced stages. IHC is a sensitive, but less specific method and the results need to be confirmed with another method like FISH or NGS. CI - (c) 2023. The Author(s). FAU - Dyrbekk, Anne Pernille Harlem AU - Dyrbekk APH AD - University of Oslo, NO-0316, Oslo, Norway. a.p.h.dyrbekk@studmed.uio.no. AD - Department of Pathology, Vestfold Hospital Trust, NO-3103, Tonsberg, Norway. a.p.h.dyrbekk@studmed.uio.no. AD - Department of Cancer Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, NO-0310, Oslo, Norway. a.p.h.dyrbekk@studmed.uio.no. FAU - Warsame, Abdirashid Ali AU - Warsame AA AD - Department of Pathology, Oslo University Hospital, The Norwegian Radium Hospital, NO-0310, Oslo, Norway. FAU - Suhrke, Pal AU - Suhrke P AD - Department of Pathology, Vestfold Hospital Trust, NO-3103, Tonsberg, Norway. FAU - Ludahl, Marianne Odnakk AU - Ludahl MO AD - Department of Microbiology/ Division for Genetechnology, Vestfold Hospital Trust, NO-3103, Tonsberg, Norway. FAU - Moe, Joakim Oliu AU - Moe JO AD - Department of Internal Medicine, Vestfold Hospital Trust, NO-3103, Tonsberg, Norway. FAU - Eide, Inger Johanne Zwicky AU - Eide IJZ AD - University of Oslo, NO-0316, Oslo, Norway. AD - Department of Cancer Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, NO-0310, Oslo, Norway. AD - Department of Oncology, Vestre Viken Hospital Trust, NO-3004, Drammen, Norway. FAU - Lund-Iversen, Marius AU - Lund-Iversen M AD - Department of Pathology, Oslo University Hospital, The Norwegian Radium Hospital, NO-0310, Oslo, Norway. FAU - Brustugun, Odd Terje AU - Brustugun OT AD - University of Oslo, NO-0316, Oslo, Norway. AD - Department of Cancer Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, NO-0310, Oslo, Norway. AD - Department of Oncology, Vestre Viken Hospital Trust, NO-3004, Drammen, Norway. LA - eng PT - Journal Article DEP - 20230527 PL - England TA - Diagn Pathol JT - Diagnostic pathology JID - 101251558 RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - 0 (Proto-Oncogene Proteins) RN - EC 2.7.10.1 (ROS1 protein, human) SB - IM MH - Humans MH - Protein-Tyrosine Kinases/genetics/metabolism MH - In Situ Hybridization, Fluorescence/methods MH - Proto-Oncogene Proteins/analysis MH - Immunohistochemistry MH - Neoplasm Recurrence, Local/genetics MH - *Lung Neoplasms/pathology MH - *Carcinoma, Non-Small-Cell Lung/genetics MH - *Adenocarcinoma/genetics/pathology MH - Gene Rearrangement PMC - PMC10224579 OTO - NOTNLM OT - Immunohistochemistry OT - Lung cancer OT - NGS OT - ROS1 OT - Targeted therapy COIS- Roche diagnostics: Contracted/Support Research Grant. Pfizer: Contracted/Support Research Grant. EDAT- 2023/05/27 09:42 MHDA- 2023/05/29 06:42 PMCR- 2023/05/27 CRDT- 2023/05/26 23:40 PHST- 2022/09/01 00:00 [received] PHST- 2023/05/18 00:00 [accepted] PHST- 2023/05/29 06:42 [medline] PHST- 2023/05/27 09:42 [pubmed] PHST- 2023/05/26 23:40 [entrez] PHST- 2023/05/27 00:00 [pmc-release] AID - 10.1186/s13000-023-01357-1 [pii] AID - 1357 [pii] AID - 10.1186/s13000-023-01357-1 [doi] PST - epublish SO - Diagn Pathol. 2023 May 27;18(1):70. doi: 10.1186/s13000-023-01357-1.