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Loss of expression of the p16 INK4 /CDKN2 gene in cutaneous malignant melanoma correlates with tumor cell proliferation and invasive stage
Author(s) -
Talve Lauri,
Sauroja Ilari,
Collan Yrjö,
Punn Kari,
Ekfors Tauno
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970620)74:3<255::aid-ijc4>3.0.co;2-y
Subject(s) - loss of heterozygosity , melanoma , immunohistochemistry , tumor suppressor gene , cancer research , biology , immunostaining , mitotic index , ki 67 , proliferation index , pathology , cell cycle , cell growth , cell , mitosis , gene , carcinogenesis , medicine , immunology , allele , genetics
The G 1 /S checkpoint of the cell cycle is regulated by p16, p53 and RB tumor suppressor genes. Loss of expression of the p16 INK4 tumor suppressor protein, the product of the CDKN 2 gene, has been associated with a wide variety of human malignancies. Mutations, loss of heterozygosity and deletions of the CDKN 2 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 G 1 /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.