Jose Luis Leal1, Geoffrey Peters2, Marcin Szaumkessel3, Trishe Leong4, Khashayar Asadi5, Gareth Rivalland3, Hongdo Do6, Clare Senko7, Paul L Mitchell7, Chai Zi Quing3, Alexander Dobrovic8, Bibhusal Thapa9, Thomas John10. 1. Department of Medical Oncology, Austin Health, Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Victoria, Australia; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. 2. ANU Medical School, Australian National University, Australian Capital Territory, Australia; Department of Medical Oncology, The Canberra Hospital, Australian Capital Territory, Australia. 3. Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia. 4. Department of Anatomical Pathology, Austin Health, Heidelberg, Victoria, Australia; Department of Anatomical Pathology, St Vincent's Hospital, Fitzroy, Victoria, Australia. 5. Department of Anatomical Pathology, Austin Health, Heidelberg, Victoria, Australia. 6. Department of Anatomical Pathology, St Vincent's Hospital, Fitzroy, Victoria, Australia. 7. Department of Medical Oncology, Austin Health, Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Victoria, Australia. 8. Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia; University of Melbourne Department of Surgery, Austin Health, Heidelberg, Victoria, Australia. 9. Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia; Department of Cardiothoracic Vascular Surgery, Manmohan Cardiothoracic Vascular and Transplant Centre, Kathmandu, Nepal. 10. Department of Medical Oncology, Austin Health, Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Victoria, Australia; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia. Electronic address: tom.john@petermac.org.
Abstract
OBJECTIVES: Gene rearrangements involving NTRK1, NTRK2, NTRK3, ROS1 and ALK have been identified in many types of cancer, including non-small cell lung cancer (NSCLC). Data in malignant pleural mesothelioma (MPM), lung neuroendocrine tumors (NETs) and small-cell lung cancer (SCLC) are lacking. Given the activity of NTRK, ROS-1 and ALK inhibitors in tumors harboring gene fusions, we sought to explore such rearrangements in these less common tumors in addition to NSCLC. METHODS: Archival tumor tissue from patients with MPM, lung NETs, SCLC and NSCLC were used to create tissue microarrays. Immunohistochemistry (IHC) was performed using a cocktail of antibodies against TRK, ROS1 and ALK. IHC positive samples underwent RNA sequencing using the ArcherDX FusionPlex CTL diagnostic assay. Clinical data were obtained through retrospective chart review. RESULTS: We performed IHC on 1116 samples: 335 MPMs, 522 NSCLCs, 105 SCLCs and 154 lung NETs. There were 23 IHC positive cases (2.1%) including eight MPMs (2.4%), eight NETs (5.2%), five SCLC (4.8%) and two NSCLC (0.4%). The following fusions were detected: one MPM with an NTRK ex10-TPM3 ex8, another MPM with an ALK ex20-EML4ex13, one lung intermediate-grade NET (atypical carcinoid) with an ALK ex20-EML4 ex6/intron6, and two NSCLCs with an ALK ex20-EML4 ex6/intron6 rearrangement. None of the patients received targeted treatment. CONCLUSIONS: To our knowledge, we report for the first time NTRK and ALK rearrangements in a small subset of MPM. An ALK rearrangement was also detected in lung intermediate-grade NET (or atypical carcinoid). Our data suggest that IHC could be a useful screening test in such patients to ensure that all therapeutic strategies including targeted therapy are utilized.
OBJECTIVES: Gene rearrangements involving NTRK1, NTRK2, NTRK3, ROS1 and ALK have been identified in many types of cancer, including non-small cell lung cancer (NSCLC). Data in malignant pleural mesothelioma (MPM), lung neuroendocrine tumors (NETs) and small-cell lung cancer (SCLC) are lacking. Given the activity of NTRK, ROS-1 and ALK inhibitors in tumors harboring gene fusions, we sought to explore such rearrangements in these less common tumors in addition to NSCLC. METHODS: Archival tumor tissue from patients with MPM, lung NETs, SCLC and NSCLC were used to create tissue microarrays. Immunohistochemistry (IHC) was performed using a cocktail of antibodies against TRK, ROS1 and ALK. IHC positive samples underwent RNA sequencing using the ArcherDX FusionPlex CTL diagnostic assay. Clinical data were obtained through retrospective chart review. RESULTS: We performed IHC on 1116 samples: 335 MPMs, 522 NSCLCs, 105 SCLCs and 154 lung NETs. There were 23 IHC positive cases (2.1%) including eight MPMs (2.4%), eight NETs (5.2%), five SCLC (4.8%) and two NSCLC (0.4%). The following fusions were detected: one MPM with an NTRK ex10-TPM3 ex8, another MPM with an ALK ex20-EML4ex13, one lung intermediate-grade NET (atypical carcinoid) with an ALK ex20-EML4 ex6/intron6, and two NSCLCs with an ALK ex20-EML4 ex6/intron6 rearrangement. None of the patients received targeted treatment. CONCLUSIONS: To our knowledge, we report for the first time NTRK and ALK rearrangements in a small subset of MPM. An ALK rearrangement was also detected in lung intermediate-grade NET (or atypical carcinoid). Our data suggest that IHC could be a useful screening test in such patients to ensure that all therapeutic strategies including targeted therapy are utilized.
Authors: Pedram Argani; Derrick W Q Lian; Abbas Agaimy; Markus Metzler; Sara E Wobker; Andres Matoso; Jonathan I Epstein; Yun-Shao Sung; Lei Zhang; Cristina R Antonescu Journal: Am J Surg Pathol Date: 2021-05-01 Impact factor: 6.298
Authors: Marco Volante; Ozgur Mete; Giuseppe Pelosi; Anja C Roden; Ernst Jan M Speel; Silvia Uccella Journal: Endocr Pathol Date: 2021-02-27 Impact factor: 3.943