title: Malignant melanoma in patients with hereditary nonpolyposis colorectal cancer.
abstract: BACKGROUND
  Malignant melanoma (MM) is the most aggressive skin cancer. Most MMs are sporadic, and in this setting an association with mismatch repair (MMR) gene mutations, typical of hereditary nonpolyposis colorectal cancer (HNPCC) tumours, has been proposed.
  
  
  OBJECTIVE
  To characterize clinically and/or by molecular biology the patients with MM belonging to a cohort of 60 kindreds with HNPCC. Methods Patients with HNPCC with a diagnosis of MM were studied by immunohistochemistry (IHC) on tumour tissue using antibodies to MLH1, MSH2, p16, beta-catenin and E-cadherin, and by direct sequencing of MMR genes on germline DNA, and BRAF and NRAS on somatic DNA extracted from MM.
  
  
  RESULTS
  Nine cutaneous MMs were detected in the tumour spectrum of eight families with HNPCC. The median age at diagnosis was 46 years. In one HNPCC family the diagnosis of MM was made in two first-degree relatives fitting the clinical definition of familial melanoma. IHC and sequencing analysis showed an MSH2 mutation in one patient with MM.
  
  
  CONCLUSIONS
  Dermatological surveillance should be recommended to families in which MM is diagnosed in at least one member, especially at a young age. The combination of MMR gene mutations and abnormalities of p16 or other molecular pathways is needed to induce melanocytic carcinogenesis in a familial setting as well as in sporadic MM.
authors.affiliation: Department of Oncology and Haematology, University of Modena and Reggio Emilia, 41100 Modena, Italy. ponti.giovanni@unimo.it
authors.forename: G
authors.initials: G
authors.lastname: Ponti
authors.forename: L
authors.initials: L
authors.lastname: Losi
authors.forename: G
authors.initials: G
authors.lastname: Pellacani
authors.forename: L
authors.initials: L
authors.lastname: Wannesson
authors.forename: A M
authors.initials: AM
authors.lastname: Cesinaro
authors.forename: T
authors.initials: T
authors.lastname: Venesio
authors.forename: C
authors.initials: C
authors.lastname: Petti
authors.forename: S
authors.initials: S
authors.lastname: Seidenari
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020137:Base Pair Mismatch / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism; D053842:Microsatellite Instability; D008875:Middle Aged; D010375:Pedigree; D011237:Predictive Value of Tests; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins