Reduced levels of the cell-cycle inhibitor p27(Kip1) in epithelial dysplasia and carcinoma of the oral cavity

Richard C.K. Jordan, Grace Bradley, Joyce Slingerland

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Abstract

Recent studies have shown that the cyclin-dependent kinase (cdk) inhibitors play important roles in cell cycle progression in normal cells. Alterations in the cdk inhibitors also appear to be important in cancer development in a number of human tumors. p27(Kip1) is a member of the CIP/KIP family of cdk inhibitors that negatively regulates cyclin-cdk complexes. Reduced levels of p27(Kip1) protein have been identified in a number of human cancers, and in some cases reduced p27(Kip1) is associated with an increase in proliferative fraction. In the present study, we examined p27(Kip1) protein by immunohistochemistry in 10 normal and 36 dysplastic epithelia and in 8 squamous cell carcinomas from one anatomical site within the oral cavity, the floor of the mouth. Proliferative activity was assessed in serial sections by determining the expression of the cell cycle proteins Ki-67 and cyclin A. p27(Kip1) protein was significantly reduced in oral dysplasias and carcinomas compared with that in normal epithelial controls. In addition, there was a significant reduction in p27(Kip1) protein between low- and high- grade dysplasias, suggesting that changes in p27(Kip1) expression may be an early event in oral carcinogenesis. There was increasing expression of Ki-67 and cyclin A proteins with increasingly severe grades of dysplasia compared with normal controls. Although there was a strong correlation between Ki-67 and cyclin A scores (r2= 0.61) for all categories of disease, there was a weak negative correlation between Ki-67 and p27(Kip1) levels (r2= 0.29) and between cyclin A and p27(Kip1) levels (r2 = 0.25). In conclusion, this study has found that a reduction in the proportion of cells expressing p27(Kip1) protein is frequently associated with oral dysplasia and carcinoma from the floor of the mouth. Furthermore, reductions in p27(Kip1) levels are associated with increased cell proliferation, although other changes likely contribute to altered cell kinetics during carcinogenesis at this site.

Original languageEnglish (US)
Pages (from-to)585-590
Number of pages6
JournalAmerican Journal of Pathology
Volume152
Issue number2
StatePublished - Feb 1 1998
Externally publishedYes

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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