Prognostic value of cyclin D1 overexpression in correlation with pRb and p53 status in non-small cell lung cancer (NSCLC)

Purpose: The aim of this study was to assess the impact of cyclin D1 overexpression ( considered separately or jointly with previously assessed p53 and pRb statuses) on survival in a group of 111 surgically treated non-small cell lung cancer patients (NSCLC). Methods: Cyclin D1 accumulation was assessed immunohistochemically, with the use of monoclonal antibody (DCS-6, DakoCytomation) and the alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. Results: Overexpression of cyclin D1 was found in 55 samples (49%), whereas the altered phenotypes cyclin D1+/p53+ or cyclin D1+/pRb- were found in 23 (22%) and 9 samples (9%), respectively. Statistical analysis was performed for different cut-off values and the only significant differences were found if samples with some expression of each protein were considered positive. There was no relationship between cyclin D1 overexpression and major clinicopathological factors, including p53 expression; however, there was a direct correlation between cyclin D1 and pRb protein expression ( p = 0.007). Cyclin D1 accumulation did not influence patients' survival. Of all possible cyclin D1/p53, cyclin D1/pRb and cyclin D1/p53/ pRb phenotypes, patients with cyclin D1 -/ p53+ phenotype had shortened overall survival compared to other patients ( p = 0.027, HR = 1.8). In the multivariate analysis, the only variable associated with shortened overall and disease-free survival was the stage of disease (p< 0.001). Conclusions: These results suggest the lack of prognostic value of cyclin D1 overexpression in NSCLC patients.