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Loss of expression of thep16INK4/CDKN2 gene in cutaneous malignant melanoma correlates with tumor cell proliferation and invasive stage

1997; Wiley; Volume: 74; Issue: 3 Linguagem: Inglês

10.1002/(sici)1097-0215(19970620)74

1097-0215

Lauri Talve, Ilari Sauroja, Yrjö Collan, Kari Punnonen, T Ekfors,

Bladder and Urothelial Cancer Treatments

AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract The G1/S checkpoint of the cell cycle is regulated by p16, p53 and RB tumor suppressor genes. Loss of expression of the p16INK4 tumor suppressor protein, the product of the CDKN2 gene, has been associated with a wide variety of human malignancies. Mutations, loss of heterozygosity and deletions of the CDKN2 locus have been reported in sporadic and familial cutaneous malignant melanomas (CMM). To investigate the role of the alterations of p16 expression in melanoma, we evaluated by immunohistochemistry the p16 expression and cell proliferation in 79 primary CMM and 10 benign melanocytic nevi (BMN). Forty-six melanomas (58%) and all BMN were found to be p16 positive; 33 melanomas (42%) were considered p16 negative. The extent of invasion according to Clark was significantly higher in p16-negative tumors than in p16-positive tumors. Cell proliferation as expressed by the proportion of positive cells in Ki-67 immunostaining was found to be significantly higher in p16-negative tumors than in p16-positive tumors, although there was no significant difference in the mitotic index between p16-positive and p16-negative tumors. In p16-positive tumors, the number of Ki-67-positive cells correlated with the mitotic index; in p16-negative tumors, there was no correlation between these parameters. Our data suggest that loss of p16 expression is more common in advanced melanomas, and that G1/S checkpoint regulation is disrupted in p16-negative melanomas. Our results show that loss of p16 expression is a common event in primary melanomas, which further substantiates the role of p16 as a major tumor suppressor. Int. J. Cancer 74:255-259, 1997. © 1997 Wiley-Liss, Inc. References Arap, W., Nishikawa, R., Furnari, F. B., Cavenee, W. K. and Huang, H.-J. S., Replacement of the p16/CDKN2 gene suppresses human glioma cell growth. Cancer Res., 55, 1351– 1354 (1995). Cairns, P. and 20 others: Frequency of homozygous deletion at p16/ CDKN2 in primary human tumours. Nature (Genet.), 11, 210– 212 (1995). Collan, Y., General principles of grading lesions in diagnostic histopathology. Pathol. Res. Pract., 185, 539– 543 (1989). Geradts, J., Kratzke, R. A., Niehans, G. A. and Lincoln, C. 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Citing Literature Volume74, Issue320 June 1997Pages 255-259 ReferencesRelatedInformation