title: Loss of p16 expression is associated with histological features of melanoma invasion.
abstract: While mutations of CDKN2A are associated with melanoma predisposition, the precise role of its gene product p16 in the development of sporadic melanoma is less clearly understood. We sought to determine the prevalence of p16 expression using immunohistochemical analysis in a population-based sample of melanoma tumours, and also to identify histological, phenotypic and environmental factors associated with the presence or absence of p16 expression. We conducted face-to-face interviews with 108 patients newly diagnosed with melanoma to ascertain their history of sun exposure, and recorded various phenotypic parameters. Paraffin sections of tumours from these patients were stained with an anti-p16 monoclonal antibody following antigen retrieval. Overall, 52 (48%) tumours expressed p16; nodular melanomas had significantly lower levels of p16 immunoreactivity than superficial spreading melanomas (P = 0.015). While no association was found between p16 expression and host phenotype, loss of p16 staining was associated with thicker lesions (p = 0.084) and a high mitotic index (P = 0.013). Taken together, these findings are consistent with loss of p16 being a late event in the progression of sporadic primary melanomas, being associated with tumours of a more aggressive nature.
authors.affiliation: Joint Experimental Oncology Programme of the Queensland Institute of Medical Research, the University of Queensland and the Queensland Cancer Fund, Post Office Royal Brisbane Hospital, Australia. sandraP@qimr.edu.au
authors.forename: S J
authors.initials: SJ
authors.lastname: Pavey
authors.forename: M C
authors.initials: MC
authors.lastname: Cummings
authors.forename: D C
authors.initials: DC
authors.lastname: Whiteman
authors.forename: M
authors.initials: M
authors.lastname: Castellano
authors.forename: M D
authors.initials: MD
authors.lastname: Walsh
authors.forename: B G
authors.initials: BG
authors.lastname: Gabrielli
authors.forename: A
authors.initials: A
authors.lastname: Green
authors.forename: N K
authors.initials: NK
authors.lastname: Hayward
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D008940:Mitotic Index; D009361:Neoplasm Invasiveness / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins