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Positive correlation between p27Kip1 expression and progression of human esophageal squamous cell carcinoma
T Anayama1, M Furihata, T Ishikawa
1Department of Pathology II, Kochi Medical School, Nankoku Kochi, Japan.
Abstract:
p27Kip1, one of the cyclin-dependent kinase (CDK) inhibitors (CDKIs), blocks progression from G1 to S phase by binding cyclin D1-CDK4 and/or cyclin E-CDK2 and inhibiting their activities. Reflecting the function of p27 as a CDKI in vitro, a reduced expression of protein p27 has recently been reported to be associated with tumor aggressiveness in some types of human cancers. In the present study, we examined the relationships between immunohistochemically detected expression of p27, cyclin D1, cyclin E proteins and clinicopathological findings in 77 patients with esophageal squamous cell carcinoma (SCC). Using specific monoclonal antibodies to p27, cyclin DI and cyclin E proteins, positive immunostaining in the nuclei was observed in 32.5% (25/77), 27.3% (21177) and 29.6% (21/71) of patients, respectively. There were no statistically significant relationships among the expressions of these 3 proteins. Using the Kaplan-Meier's method, p27 and cyclin D1 expressions were found to be independently associated with poor prognosis. When all parameters were combined into a multivariate regression analysis using the Cox model, the expressions of p27 and cyclin D1 retained a predictive value for survival. In contrast to former reports supporting a tumor-suppressive function of p27, our results suggest that altered expression of p27 and cyclin D1 may be associated with the progression of human esophageal SCC, in which cyclin E may well not play any central role.
Insights
Altered expression of p27 and cyclin D1 is linked to poorer survival in esophageal squamous cell carcinoma (SCC). These findings suggest a role in tumor progression, contrasting with p27
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- p27Kip1 is a cyclin-dependent kinase inhibitor (CDKI) that regulates cell cycle progression.
- Reduced p27 expression is linked to aggressiveness in some cancers.
- The role of p27, cyclin D1, and cyclin E in esophageal squamous cell carcinoma (SCC) requires further investigation.
Purpose of the Study:
- To investigate the relationship between p27, cyclin D1, and cyclin E protein expression and clinicopathological features in esophageal SCC.
- To determine the prognostic significance of these proteins in esophageal SCC patients.
Main Methods:
- Immunohistochemistry was used to detect p27, cyclin D1, and cyclin E protein expression in 77 esophageal SCC tumor samples.
- Kaplan-Meier survival analysis and Cox regression models were employed to assess prognostic value.
Main Results:
- Positive nuclear expression was observed for p27 (32.5%), cyclin D1 (27.3%), and cyclin E (29.6%).
- No significant correlations were found among the expression levels of the three proteins.
- Both p27 and cyclin D1 expression were independently associated with poor prognosis in esophageal SCC.
- Multivariate analysis confirmed the predictive value of p27 and cyclin D1 for patient survival.
Conclusions:
- Altered expression of p27 and cyclin D1 may contribute to the progression of esophageal SCC.
- The findings challenge the established tumor-suppressive role of p27 in this context.
- Cyclin E does not appear to play a central role in the progression of esophageal SCC.