1. Increased risk of brain metastases among patients with melanoma and PROM2 expression in metastatic lymph nodes
- Author
-
Céleste Lebbé, Barouyr Baroudjian, Julie Delyon, Christophe Lebœuf, Samia Mourah, Thuy Thi Nguyen, Anne Janin, F. Pamoukdjian, Justine Paris, Pauline Tétu, Maxime Battistella, Morad El Bouchtaoui, Jean-Paul Feugeas, Guilhem Bousquet, Guillaume Gapihan, Service d'Oncologie Médicale [AP-HP Hôpital Avicenne], Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, National Cancer Hospital K1 [Hanoi, Vietnam] (NCHK1), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Dermatologie [AP-HP Hôpital Saint-Louis], service d'Oncologie Gériatrique [Hôpital Avicenne - APHP], Hôpital Avicenne [AP-HP], Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Ecologie et Evolution des Microorganismes (EEM), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire de pathologie [AP-HP Hôpital Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Ratajczak, Philippe
- Subjects
Oncology ,medicine.medical_specialty ,Medicine (General) ,[SDV.BIO]Life Sciences [q-bio]/Biotechnology ,MEDLINE ,Medicine (miscellaneous) ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Letter to Editor ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,R5-920 ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Internal medicine ,medicine ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,0303 health sciences ,business.industry ,Melanoma ,medicine.disease ,[SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,[SDV.BIO] Life Sciences [q-bio]/Biotechnology ,3. Good health ,[SDV.TOX] Life Sciences [q-bio]/Toxicology ,Increased risk ,030220 oncology & carcinogenesis ,[SDV.TOX]Life Sciences [q-bio]/Toxicology ,Molecular Medicine ,Lymph ,business - Abstract
Background: Melanoma brain metastases are the main cause of specific death among patients with metastatic melanoma. The biology of melanoma brain metastases remains largely to be deciphered, as there have been only a few genomic studies on brain metastatic samples. In this study, melanoma metastatic lymph nodes were used with the aim to identify biomarkers associated with the occurrence of brain metastases. Methods: Fifty-one patients with melanoma lymph node metastasis and a median follow-up of 48 months were included in the development cohort. Transcriptomic data were obtained from these metastatic lymph nodes and patients who developed brain metastases and those who did not were compared. Recommendations for tumour marker prognostic studies (REMARK recommendations) were followed.Results: From transcriptomic data, we identified PROM2 which was significantly overexpressed in metastatic lymph nodes of patients who developed brain metastases compared to those who did not. Using immunohistochemistry with two different anti-PROM2 antibodies, a PROM2 score was developed for metastatic lymph nodes. Using a cut-off of 5, a PROM2 mean score ≥5 was significantly associated with an increased risk of brain metastases and an increased hazard risk of death by 4.These results were confirmed in an internal validation cohort of 50 additional patients with melanoma lymph node metastases.Conclusions: In this study, we identified PROM2 expression as a biomarker predictive of the occurrence of distant metastases, particularly brain metastases, among patients with stage III melanoma. Our findings open new perspectives to validate PROM2 as a useful biomarker for clinical trials in the adjuvant setting, and as a potential biotarget for the treatment of metastatic melanoma.
- Published
- 2020
- Full Text
- View/download PDF