Loss of p14ARF expression in melanoma

Lack of p14(ARF) expression or its functional inactivation has been observed in human and murine carcinomas. Although very few mutations of p14(ARF) have been detected in some cancer types, changes in expression seem to play an important role in the development of other human cancers such as mesotheliomas. To examine the p14(ARF) gene and expression of p14(ARF) protein in melanomas, we screened eight human melanoma cell lines and primary human melanocytes by RT-PCR, sequencing and immunoblotting. All melanoma cell lines analyzed expressed wild-type p14(ARF) mRNA as well as protein. P14(ARF) expression was investigated by immunohistochemical staining of 32 tissue samples of benign melanocytic nevi (n=14), melanomas (n=12) and melanoma metastases (n=6). In contrast to the results obtained from cell lines in vitro the immunohistochemical stainings revealed a correlation between the progression of melanoma and the lack of the p14(ARF) protein expression. Positive p14(ARF) protein staining was observed in 11 of 14 benign nevi, in 3 of 12 melanomas and in 0 of 6 melanoma metastases. In summary, we demonstrated a significant inverse correlation between p14(ARF) protein expression and progression of melanocytic tumors since the amount of p14(ARF) protein staining decreased from benign melanocytic nevi to metastatic melanoma in situ. These results suggest that p14(ARF) inactivation is important in the development of melanomas.