title: Translational significance of Nodal, Cripto-1 and Notch4 in adult nevi.
abstract: The TGF-β associated growth factor Nodal is highly expressed in aggressive metastatic melanoma. Determining the risk for melanomagenesis from Nodal expression in nevi prior to the development of melanoma may be useful for both the screening and prevention of melanoma. Tissue sections of human adult nevi with or without a history of melanoma were stained by immunohistochemistry (IHC) for Nodal, the Nodal co-receptor Cripto-1, and Notch4, which have previously been shown to be associated with Nodal expression in melanoma. The degree of Nodal, Cripto-1 and Notch4 staining was scored and correlated with available clinical data. Median IHC scores for Nodal, Cripto-1 and Notch4 expression were significantly higher in nevi removed from patients who eventually developed melanoma compared with nevi from patients with no history of melanoma. In addition, the degree of Nodal expression in nevi from patients who eventually developed melanoma correlated significantly with the Breslow depth of the melanoma. Expression of Nodal and components of its signaling pathway in nevi may represent a biomarker for selecting a unique subset of patients requiring increased surveillance for screening and prevention of melanoma.
authors.affiliation: Cancer Biology and Epigenomics Program, Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Strizzi
authors.affiliation: Cancer Biology and Epigenomics Program, Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
authors.forename: Naira V
authors.initials: NV
authors.lastname: Margaryan
authors.affiliation: Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Pedram
authors.initials: P
authors.lastname: Gerami
authors.affiliation: Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Haghighat
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Harms
authors.affiliation: Melanoma, Cancer Immunotherapy and Innovative Therapy Unit, Istituto Nazionale Tumori Fondazione Pascale, 80131 Napoli, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Madonna
authors.affiliation: Department of Pathology, Istituto Nazionale Tumori Fondazione Pascale, 80131 Napoli, Italy.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.affiliation: Melanoma, Cancer Immunotherapy and Innovative Therapy Unit, Istituto Nazionale Tumori Fondazione Pascale, 80131 Napoli, Italy.
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Ascierto
authors.affiliation: Cancer Biology and Epigenomics Program, Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Mary J C
authors.initials: MJ
authors.lastname: Hendrix
keywords: Cripto-1; Nodal; Notch4; biomarker; immunohistochemistry; melanoma; nevus; screening