title: Expression and localization of mutant p16 proteins in melanocytic lesions from familial melanoma patients.
abstract: Little is known about the correlation between the loss of p16 expression and tumor progression in familial melanoma; no systematic study has been conducted on p16 expression in melanocytic tumors from patients carrying germline CDKN2A mutations. We analyzed 98 early primary lesions from familial patients, previously tested for germline CDKN2A status, by quantitative immunohistochemistry using 3 p16 antibodies. We found that p16 expression was inversely correlated with tumor progression and was significantly lower in melanomas, including in situ lesions, than in nevi. Of other features analyzed, tumor thickness showed the most significant correlation with p16 levels. Lesions from mutation-negative patients displayed combined nuclear and cytoplasmic staining. However, some mutation-positive lesions (ie, G101W, 113insR, M53I, R24P, and 33ins24), including benign nevi, showed nuclear mislocalization, confirming previous studies suggesting that subcellular distribution indicates functional impairment of p16.
authors.affiliation: Department of Oncology, Biology, and Genetics, University of Genova, Genova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Ghiorzo
authors.forename: Barbara
authors.initials: B
authors.lastname: Villaggio
authors.forename: Angela Rita
authors.initials: AR
authors.lastname: Sementa
authors.forename: Johan
authors.initials: J
authors.lastname: Hansson
authors.forename: Anton
authors.initials: A
authors.lastname: Platz
authors.forename: Guido
authors.initials: G
authors.lastname: Nicoló
authors.forename: Bruno
authors.initials: B
authors.lastname: Spina
authors.forename: Marco
authors.initials: M
authors.lastname: Canepa
authors.forename: Jane M
authors.initials: JM
authors.lastname: Palmer
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Hayward
authors.forename: Giovanna
authors.initials: G
authors.lastname: Bianchi-Scarrà
mesh_terms: D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D009506:Nevus / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D025803:Tumor Suppressor Protein p14ARF