Expressions of Cyclin E-pathway Proteins (cyclinE, cdk2, p21, p27, p57) and Their Prognostic Significance in Non-small Cell Lung Carcinomas

ABSTRACT

BACKGROUND: The aberrant expression of cyclins, cdk and cdk inhibitor has been shown to be involved in oncogenic transformation. The aim of this study was to investigate the expression of the cyclin E-pathway proteins (cyclin E, cdk2, p21, p27, p57) in human non-small cell lung carcinomas (NSCLC) and also to evaluate the clinical significance of these expressions. METHODS: A total of 203 consecutive patients with completely resected pathological stage I-III NSCLC were retrospectively reviewed. The expressions of cyclin E, cdk2, p21, p27 and, p57 was examined by performing immunohistochemistry with using the tissue microarray method. RESULTS: In the total cases, the expression levels of cyclin E, cdk2, p21, p27 and p57 were 39.9% (81/203), 48.3% (98/203), 68.0% (138/203), 32.5% (66/203) and 2.7% (5/203), respectively. The overexpression of cyclin E and cdk2 was significantly and inversely correlated with the histologic differentiation in the adenocarcinoma (p<0.05), but not in the squamous cell carcinoma. Among the clinicopathologic factors, the stage and lymph node metastasis were associated with overall survival (p<0.05). Among these proteins, the negative expression of p21 was significantly correlated with a shortened survival rate (p<0.05). CONCLUSIONS: These data suggest that the overexpression of cyclin E and cdk2 and the loss of p21 and p27 are associated with tumor progression in NSCLC. The aberrant expression of p21 is correlated with a poor prognosis. Therefore the immunohistochemical analysis of this protein as well as the clinical stage and, lymph node metastasis may be useful tools for evaluating the prognosis of NSCLC patients.