title: Histologic features of melanoma associated with CDKN2A genotype.
abstract: BACKGROUND
  Inherited susceptibility genes have been associated with histopathologic characteristics of tumors.
  
  
  OBJECTIVE
  We sought to identify associations between histology of melanomas and CDKN2A genotype.
  
  
  METHODS
  This was a case-control study design comparing 28 histopathologic tumor features among individuals with sporadic melanomas (N = 81) and cases from melanoma families with (N = 123) and without (N = 120) CDKN2A germline mutations.
  
  
  RESULTS
  Compared with CDKN2A(-) cases, mutation carriers tended to have histologic features of superficial spreading melanoma subtype including higher pigmentation (Ptrend = .02) and increased pagetoid scatter (Ptrend = .07) after adjusting for age at diagnosis, sex, and American Joint Committee on Cancer thickness category. Similar associations were observed when comparing mutation carriers with a combined group of CDKN2A(-) (wild type) and sporadic melanomas. The presence of spindle cell morphology in the vertical growth phase was also an important predictor of genotype. Of the 15 cases with this phenotype, none were observed to harbor a CDKN2A mutation.
  
  
  CONCLUSIONS
  Our study examined rare mutations and may have been underpowered to detect small, but biologically significant associations between histology and genotype.
  
  
  CONCLUSIONS
  Familial melanomas with CDKN2A mutations preferentially express a histologic phenotype of dense pigmentation, high pagetoid scatter, and a non-spindle cell morphology in the vertical growth phase.
authors.affiliation: Department of Dermatology, Emory University Hospital, Atlanta, Georgia. Electronic address: michael.sargen@emory.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Sargen
authors.affiliation: Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kanetsky
authors.affiliation: Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, Leeds, United Kingdom.
authors.forename: Julia
authors.initials: J
authors.lastname: Newton-Bishop
authors.affiliation: Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Hayward
authors.affiliation: University of Sydney at Westmead Millennium Institute and Melanoma Institute Australia, Sydney, Australia.
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Mann
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Nelleke A
authors.initials: NA
authors.lastname: Gruis
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Tucker
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Alisa M
authors.initials: AM
authors.lastname: Goldstein
authors.affiliation: Department of Internal Medicine and Medical Specialties (Di.M.I.) University of Genoa, Genetics of Rare Cancers, Istituto Di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliera Universitaria (IRCCS AOU) San Martino -IST, Genoa, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Bianchi-Scarra
authors.affiliation: Hospital Clinic of Barcelona, University of Barcelona, Institut de Recerca Biomédica August Pi I Sunyer, Barcelona, Spain; Centro de Investigaciones Biomédicas en Red de Enfermedades Raras, Instituto de Salud Carlos III, Barcelona, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Puig
authors.affiliation: Department of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: David E
authors.initials: DE
authors.lastname: Elder
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16
keywords: CDKN2A; classification and regression tree analysis; familial melanoma; genetic testing; histology; pagetoid scatter; pigmentation; sporadic melanoma