title: Loss of pRb2/p130 expression is associated with unfavorable clinical outcome in lung cancer.
abstract: 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.
authors.affiliation: Department of Medical-Surgical, Cardiological, Respiratory, and Thoracic Sciences, Second University of Naples, Naples, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Caputi
authors.forename: Angela M
authors.initials: AM
authors.lastname: Groeger
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Esposito
authors.forename: Antonio
authors.initials: A
authors.lastname: De Luca
authors.forename: Valeria
authors.initials: V
authors.lastname: Masciullo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mancini
authors.forename: Feliciano
authors.initials: F
authors.lastname: Baldi
authors.forename: Ernst
authors.initials: E
authors.lastname: Wolner
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
mesh_terms: D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010750:Phosphoproteins / Q000378:metabolism*; D011379:Prognosis; D011506:Proteins; D016160:Retinoblastoma Protein / Q000378:metabolism*; D050717:Retinoblastoma-Like Protein p130; D015996:Survival Rate
chemical_list: D010750:Phosphoproteins; D011506:Proteins; C493837:RBL2 protein, human; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130