p21waf1 is a downstream effector of p53, and mediates growth arrest by inhibiting the action of G1 cyclin-dependent kinases. Cyclin D1 is a cell-cycle regulator essential for G1 phases progression and a candidate proto-oncogene implicated in the pathogenesis of several human tumor types. Cyclin D1 overexpression and the absence of retinoblastoma (Rb) protein have been frequently seen in various types of cancer, including lung cancer. The aim of this study was to clarify the relationship between the expressions of p21waf1, cyclin D1, and Rb protein, and to investigate the correlation between these protein expressions and the clinical features of the patients, and their prognoses. We immunohistochemically examined 92 samples of resected non-small cell lung cancer for p21waf1, cyclin D1, and Rb expression. Of the 92 specimens examined, 43 cases (46.7%) showed p21waf1 expression, 23 cases (25.0%) showed cyclin D1 overexpression, and 61 cases (66.3%) showed Rb expression. No correlation was observed between the expressions of p21waf1, cyclin D1, and Rb. There was no association of p21waf1 and cyclin D1 immunoreactivity with gender, disease stage, or histological types of the tumor. Regarding the prognosis in 79 cases with complete resection, no statistical differences were observed according to the degree of expression of these three factors. However, when unfavorable prognostic factors were considered to be the positive expression of p21waf1, positive of cyclin D1, and negative of Rb, the 5-year disease-free survival rate in the group with 2 or 3 unfavorable prognostic factors was 21.1%, which was statistically poorer than the 45.4% in the group with 0 or 1 unfavorable prognostic factor (p=0.0138). We conclude that examination of the expression of cell cycle regulators, such as p21waf1, cyclin D1, and Rb, is useful as a prognostic indicator, when these proteins' expression is analyzed in combination.

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