Prognostic role of cyclin D1 in lung cancer - Relationship to proliferating cell nuclear antigen

We developed an immunohistochemical assay specific for cyclin D1 and suitab le for formalin-fixed and paraffin-embedded sections, to evaluate cyclin D1 expression in a group of 135 surgically resected lung-cancer patients for the purpose of investigating the prognostic role of this protein in lung ca ncer. In addition, we compared cyclin D1 expression with the expression of proliferating cell nuclear antigen (PCNA), considered to be a reliable inde x of the proliferation rate. We found cyclin D1 expressed in more than 60% of the neoplastic cells in 26.5% of our specimens. A total of 24.5% of the specimens showed cyclin D1 expression in a percentage of cells ranging from 30 to 60%; 36.7% of the specimens expressed cyclin D1 in less than 30% of the cells; and 12.2% of the specimens expressed cyclin D1 in less than 1% o f the evaluated cells. Western blot analyses confirmed the specificity of t his assay by correlating statistically in a highly significant fashion with the immunohistochemical results (P = 0.0003). Furthermore, we found a dire ct relationship between cyclin D1 and PCNA immunodetection (P = 0.0004), wh ich correlated cyclin D1 overexpression with a higher tumor proliferation r ate. When we analyzed our data statistically, cyclin D1 expression was foun d to be a negative prognostic marker (P < 0.00005) whose expression correla tes with a shorter patient survival time.