Am. J. Respir. Cell Mol. Biol., Volume 20, Number 4, April, 1999 746-750

Prognostic Role of Cyclin D1 in Lung Cancer
Relationship to Proliferating Cell Nuclear Antigen

Mario Caputi, Angela M. Groeger, Vincenzo Esposito, Charity Dean, Antonio De Luca, Carmen Pacilio, Michael R. Muller, Giovan G. Giordano, Feliciano Baldi, Ernst Wolner, and Antonio Giordano

Department of Respiratory Diseases, University of Naples, Azienda Ospedaliera Monaldi, Naples, Italy; Department of Pathology, Anatomy, and Cell Biology, Jefferson Medical College, Sbarro Institute for Cancer Research and Molecular Medicine, Philadelphia, Pennsylvania; Department of Cardio-Thoracic Surgery, University of Vienna, Vienna, Austria; and Department of Anatomic Pathology, University of Naples, Naples, Italy

We developed an immunohistochemical assay specific for cyclin D1 and suitable 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 cancer. In addition, we compared cyclin D1 expression with the expression of proliferating cell nuclear antigen (PCNA), considered to be a reliable index 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% of the evaluated cells. Western blot analyses confirmed the specificity of this assay by correlating statistically in a highly significant fashion with the immunohistochemical results (P = 0.0003). Furthermore, we found a direct relationship between cyclin D1 and PCNA immunodetection (P = 0.0004), which correlated cyclin D1 overexpression with a higher tumor proliferation rate. When we analyzed our data statistically, cyclin D1 expression was found to be a negative prognostic marker (P < 0.00005) whose expression correlates with a shorter patient survival time.

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