Expression and Localization of Mutant p16 Proteins in Melanocytic Lesions from Familial Melanoma Patients

Paola Ghiorzo, Barbara Villaggio, Angela Rita Sementa, Johan Hansson, Anton Platz, Guido Nicoló, Bruno Spina, Marco Canepa, Jane M. Palmer, Nicholas K. Hayward, Giovanna Bianchi-Scarrà

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)25-33
Number of pages9
JournalHuman Pathology
Issue number1
Publication statusPublished - Jan 2004


  • CDKN2A/p16INK4A
  • Familial melanoma
  • Immunohistochemistry
  • Localization
  • Mutation
  • Nevi

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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