Analysis of cell cycle regulator proteins in non-small cell lung cancer.

Third Division of Infective Diseases, D. Cotugno Hospital, Naples 80100, Italy.
Journal of Clinical Pathology (Impact Factor: 2.92). 02/2004; 57(1):58-63.
Source: PubMed


Abnormalities of the proteins involved in cell cycle checkpoints are extremely common among almost all neoplasms. This study aimed to investigate the expression of four components of the cell cycle machinery-p21, p16, p53, and proliferating cell nuclear antigen (PCNA)-in non-small cell lung cancer (NSCLC).
The expression of p21, p16, p53, and PCNA was examined in 68 well characterised NSCLC specimens using immunohistochemistry. The coregulation of these proteins and their influence on survival were analysed using both univariate and multivariate analyses.
By univariate analysis, the expression of all the proteins examined, except for PCNA, was significantly correlated with survival. In multivariate analysis, the only immunohistochemical parameter able to influence overall survival was p16, confirming the hypothesis that the RB-p16 tumour suppressor pathway is inactivated in most lung cancer samples. Finally, the group of patients with NSCLC who were negative for both p21 and p16 had a significantly shorter overall survival.
These results suggest that loss of control of cell cycle checkpoints is a common occurrence in lung cancers, and support the idea that functional cooperation between different cell cycle inhibitor proteins constitutes another level of regulation in cell growth control and tumour suppression.

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Available from: Alfonso Baldi
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    • "One of the most important checkpoints involved in oncogenesis is the restriction point in the late G1 stage. Defects in G1 regulatory proteins, particularly deregulation of the P53–MDM2/4(Greenblatt et al. 1994; Esposito et al. 2004) and cyclin D/CDK 4-CDKN2A (p16)-retinoblastoma (RB) protein pathways (Yoshida et al. 2004; Cheng et al. 2003), seem to be essential for the development of lung cancer. The product of the Cdkn2a gene is an inhibitor of CDK 4/6, which phosphorylates the serine/threonine residues of the tumour suppressor RB and plays an important role in inhibiting cell cycle progression (WIKENHEISER-BROKAMP, 2006). "
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    • "While several of the factors involved in regulating cell-cycle control have been investigated in lung cancer, few studies have examined multiple factors in the same tumor series. Our research group recently sets up a study to evaluate the expression of p53, p21, p16, and PCNA proteins in a large series of non-small-cell lung cancers (NSCLCs) to assess the integrity of cell-cycle checkpoints in these tumors, to evaluate the coexpression of these proteins, and, finally, to examine the relationship between these cell-cycle regulators and the clinicopathological features of NSCLCs, including their ability to predict survival in NSCLC patients [127]. When we looked at the correlation between clinicopathological data and expression of cell-cycle proteins, we found a negative correlation between lymph nodes status and p21, and p16 expression, suggesting a possible role for these two proteins in the progression of the disease. "
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    • "Only p16 had a direct impact on the 5-yr survival in patients with NSCLC. This is in agreement with the results of the study by Esposito et al. (8). In their multivariate analysis on cell cycle regulator proteins, the only immunohistochemical parameter that influenced overall survival was p16. "
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