Marius Ilie1, Elodie Long-Mira2, Elisa Funck-Brentano3, Sandra Lassalle2, Catherine Butori2, Virginie Lespinet-Fabre4, Olivier Bordone4, Alexandre Gay4, Katia Zahaf4, Gilles Poissonnet5, Jean-Philippe Lacour6, Philippe Bahadoran7, Robert Ballotti8, Audrey Gros9, Caroline Dutriaux10, Philippe Saiag3, Jean-Philippe Merlio9, Béatrice Vergier9, Jean François Emile11, Véronique Hofman1, Paul Hofman12. 1. Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France; Human Biobank BB-0033-00025, Pasteur Hospital, Nice, France. 2. Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France. 3. EA4340-Biomarqueurs en Cancérologie et Onco-Hématologie (BCOH), University of Versailles Saint-Quentin-en-Yvelines (SQY), Boulogne, France; Department of General and Oncologic Dermatology, Ambroise Paré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Boulogne, France. 4. Human Biobank BB-0033-00025, Pasteur Hospital, Nice, France. 5. Surgery Department, Comprehensive Cancer Center Antoine Lacassagne, Nice, France. 6. Dermatology Department, Archet II Hospital, Nice, France. 7. Dermatology Department, Archet II Hospital, Nice, France; Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Team 1, University of Nice Sophia Antipolis, Nice, France. 8. Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Team 1, University of Nice Sophia Antipolis, Nice, France. 9. Pathology and Molecular Biology Departments, Centre Hospitalier Universitaire (CHU) and EA2406 University of Bordeaux, Bordeaux, France. 10. Department of Oncologic Dermatology, CHU Bordeaux, Bordeaux, France. 11. EA4340-Biomarqueurs en Cancérologie et Onco-Hématologie (BCOH), University of Versailles Saint-Quentin-en-Yvelines (SQY), Boulogne, France; Department of Pathology, Ambroise Paré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Boulogne, France. 12. Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France; Human Biobank BB-0033-00025, Pasteur Hospital, Nice, France. Electronic address: hofman.p@chu-nice.fr.
Abstract
BACKGROUND: It can be useful to assess the NRAS mutation status in patients with metastatic melanoma because NRAS-activating mutations confer resistance to RAF inhibitors, and NRAS-mutated patients appear to be sensitive to mitogen-activated protein kinase (MEK) inhibitors. OBJECTIVE: We aimed to assess the diagnostic accuracy of an immunohistochemistry (IHC) approach using a novel anti-NRAS (Q61R) monoclonal antibody on formalin-fixed paraffin-embedded tissue samples from patients with metastatic melanoma. METHODS: We conducted a retrospective multicenter cohort study on 170 patients with metastatic melanoma. The automated IHC assay was performed using the SP174 clone, and compared with results of the molecular testing. RESULTS: Evaluation of a test cohort with knowledge of the mutation status established a specific IHC pattern for the mutation. In the independent blinded analysis of the remaining cases, the anti-NRAS (Q61R) antibody accurately identified all NRAS Q61R-mutated tumors, and demonstrated 100% sensitivity and specificity. LIMITATIONS: Limitations include retrospective design and lack of multicenter interobserver reproducibility. CONCLUSION: The NRAS (Q61R) IHC assay is reliable and specific for the evaluation of the Q61R mutation status in metastatic melanoma and may be an alternative to molecular biology in evaluation of metastatic melanoma in routine practice.
BACKGROUND: It can be useful to assess the NRAS mutation status in patients with metastatic melanoma because NRAS-activating mutations confer resistance to RAF inhibitors, and NRAS-mutated patients appear to be sensitive to mitogen-activated protein kinase (MEK) inhibitors. OBJECTIVE: We aimed to assess the diagnostic accuracy of an immunohistochemistry (IHC) approach using a novel anti-NRAS (Q61R) monoclonal antibody on formalin-fixed paraffin-embedded tissue samples from patients with metastatic melanoma. METHODS: We conducted a retrospective multicenter cohort study on 170 patients with metastatic melanoma. The automated IHC assay was performed using the SP174 clone, and compared with results of the molecular testing. RESULTS: Evaluation of a test cohort with knowledge of the mutation status established a specific IHC pattern for the mutation. In the independent blinded analysis of the remaining cases, the anti-NRAS (Q61R) antibody accurately identified all NRASQ61R-mutated tumors, and demonstrated 100% sensitivity and specificity. LIMITATIONS: Limitations include retrospective design and lack of multicenter interobserver reproducibility. CONCLUSION: The NRAS (Q61R) IHC assay is reliable and specific for the evaluation of the Q61R mutation status in metastatic melanoma and may be an alternative to molecular biology in evaluation of metastatic melanoma in routine practice.
Authors: Anna Felisiak-Goląbek; Shingo Inaguma; Artur Kowalik; Bartosz Wasąg; Zeng-Feng Wang; Sebastian Zięba; Liliana Pięciak; Janusz Ryś; Janusz Kopczynski; Maarit Sarlomo-Rikala; Stanislaw Góźdź; Jerzy Lasota; Markku Miettinen Journal: Appl Immunohistochem Mol Morphol Date: 2018-01
Authors: Jerzy Lasota; Artur Kowalik; Anna Felisiak-Golabek; Shingo Inaguma; Zeng-Feng Wang; Liliana Pięciak; Sebastian Zięba; Rafał Pęksa; Janusz Kopczynski; Krzysztof Okoń; Piotr Waloszczyk; Stanislaw Gozdz; Wojciech Biernat; Markku Miettinen Journal: Arch Pathol Lab Med Date: 2017-02-28 Impact factor: 5.534