Expression and localization of mutant p16 proteins in melanocytic lesions from familial melanoma patients

• Published in: Human pathology 2004, Vol.35 (1), p.25-33
• Main Authors: Ghiorzo, Paola, Villaggio, Barbara, Sementa, Angela Rita, Hansson, Johan, Platz, Anton, Nicoló, Guido, Spina, Bruno, Canepa, Marco, Palmer, Jane M, Hayward, Nicholas K, Bianchi-Scarrà, Giovanna
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; CDKN2A/p16INK4A; Comparative analysis; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; Cyclin-dependent kinases; Deoxyribonucleic acid; Dermatology; DNA; familial melanoma; Family medical history; Female; Gene Expression Regulation, Neoplastic; Genes, p16; Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); Kinases; localization; Male; Medical research; Medical sciences; Medicin och hälsovetenskap; Melanocytes - metabolism; Melanocytes - pathology; Melanoma - genetics; Melanoma - metabolism; Melanoma - secondary; Molecular weight; Mutation; nevi; Nevus - genetics; Nevus - metabolism; Nevus - pathology; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Proteins; Skin Neoplasms - genetics; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; Studies; Tumor Suppressor Protein p14ARF - genetics; Tumor Suppressor Protein p14ARF - metabolism; Tumors of the skin and soft tissue. Premalignant lesions
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2003.08.017

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.