title: HER4 and its cytoplasmic isoforms are associated with progression-free survival of malignant melanoma.
abstract: HER4 belongs to the epidermal growth factor (EGF) family. Mutations in HER4 are associated with malignant melanoma. This points to HER4 as an important receptor in malignant melanoma and also raises the question of whether the other receptors in the EGF system could be involved. RT-qPCR mRNA quantification was carried out of all four EGF receptors (EGFR, HER2, HER3, and HER4) and the HER4 cytoplasmic isoforms in lymph node metastases from patients with malignant melanoma. We related their expression to progression of the disease. HER4 expression was found to be an indicator of short progression-free survival (P=0.0340). Interestingly, of the two cytoplasmic splice variants of HER4, the association of CYT1 (P=0.0176) with progression-free survival was more pronounced than that for CYT2 (P=0.0458). Also, HER3 was associated with progression-free survival (P=0.0169), whereas no association was found for EGFR or HER2 with time to progression. Our results further emphasize the role of HER4 as an important oncogene in malignant melanoma and point to HER4 as a possible drug target in this disease.
authors.affiliation: aDepartment of Clinical Biochemistry, University Hospital of Aarhus, Aarhus C bDepartment of Biomedical Sciences, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark cLaboratory of Oncology and Experimental Surgery, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Trine O
authors.initials: TO
authors.lastname: Nielsen
authors.forename: Steen S
authors.initials: SS
authors.lastname: Poulsen
authors.forename: Fabrice
authors.initials: F
authors.lastname: Journe
authors.forename: Ghanem
authors.initials: G
authors.lastname: Ghanem
authors.forename: Boe S
authors.initials: BS
authors.lastname: Sorensen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000201:enzymology* / Q000235:genetics; D008875:Middle Aged; D011379:Prognosis; D066247:Receptor, ErbB-4; D012878:Skin Neoplasms / Q000201:enzymology* / Q000235:genetics
chemical_list: D007527:Isoenzymes; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4