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PMID: 9466585 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Reduced levels of the cell-cycle inhibitor p27Kip1 in epithelial dysplasia and carcinoma of the oral cavity.

The American journal of pathology ·Vol. 152 ·No. 2 ·1998-02-00 ·Pages 585-90

Jordan RC, Bradley G, Slingerland J

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. p27Kip1 is a member of the CIP/KIP family of cdk inhibitors that negatively regulates cyclin-cdk complexes. Reduced levels of p27Kip1 protein have been identified in a number of human cancers, and in some cases reduced p27Kip1 is associated with an increase in proliferative fraction. In the present study, we examined p27Kip1 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. p27kip1 protein was significantly reduced in oral dysplasias and carcinomas compared with that in normal epithelial controls. In addition, there was a significant reduction in p27Kip1 protein between low- and high-grade dysplasias, suggesting that changes in p27Kip1 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 p27Kip1 levels (r2 = 0.29) and between cyclin A and p27Kip1 levels (r2 = 0.25). In conclusion, this study has found that a reduction in the proportion of cells expressing p27Kip1 protein is frequently associated with oral dysplasia and carcinoma from the floor of the mouth. Furthermore, reductions in p27Kip1 levels are associated with increased cell proliferation, although other changes likely contribute to altered cell kinetics during carcinogenesis at this site.

MeSH Terms
Carcinoma, Squamous Cell/metabolism,pathology Cell Cycle/drug effects Cell Cycle Proteins Cross-Sectional Studies Cyclin-Dependent Kinase Inhibitor p27 Enzyme Inhibitors/metabolism Humans Microtubule-Associated Proteins/metabolism Mouth Mucosa/metabolism,pathology Mouth Neoplasms/metabolism,pathology Retrospective Studies Tumor Suppressor Proteins
Chemicals
Cell Cycle Proteins Enzyme Inhibitors Microtubule-Associated Proteins Tumor Suppressor Proteins Cyclin-Dependent Kinase Inhibitor p27
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Jordan R C
Department of Oral Pathology, Faculty of Dentistry, University of Toronto, Ontario, Canada. richard.jordan@sunnybrook.on.ca
Bradley G
Slingerland J
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
Email
richard.jordan@sunnybrook.on.ca
Published
1998-02-00
Pages
585-90
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1857966
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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