title: p15 Expression Differentiates Nevus from Melanoma.
abstract: Most melanomas are driven by BRAF(V600E)-activating mutations, while nevi harboring the same mutations have growth arrest. Although decreased p16 expression has been associated with melanoma formation, in recent work, p15 represented a primary effector of oncogene-induced senescence in nevomelanocytes that was diminished in melanomas. This study determined whether decreased p15 levels represent a general biomarker for the transition from nevus to melanoma. We performed p15 and p16 IHC analyses on a random series of nevi and melanomas. Staining was evaluated and graded for percentage and intensity to determine the H score. For real-time quantitative RT-PCR analysis of p15, RNA was extracted from FFPE sections from 14 nevus and melanoma samples via macrodissection. A two-sided t-test was used to evaluate between-group differences in mean H scores and qΔCt values. p15 Expression was significantly increased in melanocytic nevi compared with melanomas (mean H scores, 254.8 versus 132.3; P < 0.001). On p15 staining, the H score differential was greater than that with p16 staining [122.5 (P < 0.001) and 64.8 (P = 0.055), respectively]. Real-time quantitative RT-PCR analysis revealed a lower mean qΔCt value in melanomas, consistent with lower p15 expression (P = 0.018). Together, these data support the hypothesis that decreased p15 expression is a robust biomarker for distinguishing nevus from melanoma.
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Taylor
authors.affiliation: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Conor
authors.initials: C
authors.lastname: O'Day
authors.affiliation: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Tzvete
authors.initials: T
authors.lastname: Dentchev
authors.affiliation: United States Bureau of Economic Analysis, Washington, District of Columbia.
authors.forename: Kyle
authors.initials: K
authors.lastname: Hood
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Emily Y
authors.initials: EY
authors.lastname: Chu
authors.affiliation: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Todd W
authors.initials: TW
authors.lastname: Ridky
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: john.seykora@uphs.upenn.edu.
authors.forename: John T
authors.initials: JT
authors.lastname: Seykora
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D003937:Diagnosis, Differential; D006801:Humans; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D009506:Nevus / Q000378:metabolism* / Q000473:pathology; D009508:Nevus, Pigmented / Q000378:metabolism* / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf