title: Expression of cell cycle-regulated proteins pRB2/p130, p107, E2F4, p27, and pCNA in salivary gland tumors: prognostic and diagnostic implications.
abstract: The retinoblastoma family consists of the tumor suppressor nuclear phosphoprotein pRb/p105 and related proteins p107 and pRb2/p130. Recent immunohistochemical studies of the retinoblastoma family of proteins in lung and endometrial cancer and choroidal melanomas show a tight inverse correlation between the histologic grading in the most aggressive tumor types and pRb2/p130 expression. This led us to investigate the role of pRb2/p130 in salivary tumors. We studied the expression of pRb2/p130, p107, E2F4, p27, and PcNA by immunohistochemistry in a panel of 44 salivary gland tumors. We found a direct correlation between the cytoplasmic expression of pRb2/p130 and tumor grading and the presence of metastasis that was highly statistically significant (P < 0.001). Additionally, increased cytoplasmic pRb2/p130 expression was significantly correlated with a decreased probability of survival (P < 0.001). Interestingly, p107 nuclear expression showed a strong direct correlation when compared with the same variables. pRb2/p130 showed the highest percentage of undetectable nuclear levels in the specimens examined and the tightest inverse correlation (P < 0.0001) with both the histologic grading and pCNA expression in malignant salivary tumors. Additionally, E2F4 showed an identical localization pattern as to that of pRb2/p130. These data suggests an important role for pRb2/p130 in the pathogenesis and progression of certain salivary gland cancers.
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, PA 19122-6099, USA.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Russo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Zamparelli
authors.forename: Candace M
authors.initials: CM
authors.lastname: Howard
authors.forename: Corrado
authors.initials: C
authors.lastname: Minimo
authors.forename: Cristiana
authors.initials: C
authors.lastname: Bellan
authors.forename: Giovanna
authors.initials: G
authors.lastname: Carillo
authors.forename: Luigi
authors.initials: L
authors.lastname: Califano
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Leoncini
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Claudio
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D018797:Cell Cycle Proteins / Q000032:analysis*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004268:DNA-Binding Proteins / Q000032:analysis; D050684:E2F Transcription Factors; D050704:E2F4 Transcription Factor; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011506:Proteins / Q000032:analysis; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D012468:Salivary Gland Neoplasms / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000032:analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050704:E2F4 Transcription Factor; C493762:E2F4 protein, human; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D011506:Proteins; C493844:RBL1 protein, human; C493837:RBL2 protein, human; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27