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Loss of pRb2/p130 Expression Is Associated with Unfavorable Clinical Outcome in Lung Cancer¹

Department of Medical-Surgical, Cardiological, Respiratory, and Thoracic Sciences [M. C., V. E., A. M.] and Department of Biochemistry and Biophysics "F. Cedrangolo," Section of Anatomic Pathology [F. B., E. W.], Second University of Naples, Naples, Italy; Department of Cardio-Thoracic Surgery, University of Vienna, Vienna, Austria [A. M. G.]; Laboratory for Cell Metabolism and Pharmacokinetics, Center for Experimental Research, Institute Regina Elena, Rome, Italy [A. D. L.]; Department of Pathology, Anatomy, and Cell Biology, Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, Pennsylvania [V. M., A. G.]; and Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122 [A. G.]

Altered expression of cell cycle regulators represents a frequent event in both small cell and non-small cell lung cancer (NSCLC). Despite several studies that reported involvement of tumor suppressor genes, such as p53 and pRb, in the development and progression of lung cancer, contrasting opinions exist about the prognostic role of this protein in this neoplasm. We developed an immunohistochemical assay suitable for the detection of pRb2/p130, the last discovered member of the retinoblastoma gene family, on formalin-fixed and paraffin-embedded sections. We evaluated the immunohistochemical expression of pRb2/p130 in 135 lung cancer specimens, and performed Western blot analysis in a subset of 30 corresponding tumor lysates. A high correlation between immunohistochemical data and Western blot results (P = 0.0004) was found. We statistically analyzed the relationship between overall survival (OS) time and pRb2/p130 expression according to the different histological types in 105 patients. We did not find any correlation between pRb2/p130 expression and OS in small cell lung cancers, whereas in NSCLCs a direct relationship between pRb2 and OS was found in both adenocarcinoma (P = 0.0002) and squamous cell carcinoma (P = 0.0002) histotypes. According to univariate analysis, pRb2/p130 was a prognostic factor of which the lost or reduced expression correlated with a shorter OS (P < 0.0000). At multivariate analysis, pRb2/p130 expression was an independent predictor of OS (P = 0.0001) when considered together with histotype.

This study demonstrates for the first time the potential independent prognostic value of pRb2/p130 expression on formalin-fixed, paraffin-embedded sections from lung cancer patients. pRb2/p130 immunoreactivity can be used to predict OS in patients with NSCLC and, therefore, may represent a new prognostic marker.

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