Expression of cell cycle-regulated proteins pRB2/p130, p107, E2F4, p27, and pCNA in salivary gland tumors: prognostic and diagnostic implications

Clin Cancer Res. 2005 May 1;11(9):3265-73. doi: 10.1158/1078-0432.CCR-04-2508.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Cell Cycle Proteins / analysis*
  • Cyclin-Dependent Kinase Inhibitor p27
  • DNA-Binding Proteins / analysis
  • E2F Transcription Factors
  • E2F4 Transcription Factor
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Nuclear Proteins / analysis
  • Prognosis
  • Proliferating Cell Nuclear Antigen / analysis
  • Proteins / analysis
  • Retinoblastoma-Like Protein p107
  • Retinoblastoma-Like Protein p130
  • Salivary Gland Neoplasms / metabolism
  • Salivary Gland Neoplasms / pathology*
  • Transcription Factors / analysis
  • Tumor Suppressor Proteins / analysis


  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F4 Transcription Factor
  • E2F4 protein, human
  • Nuclear Proteins
  • Proliferating Cell Nuclear Antigen
  • Proteins
  • RBL1 protein, human
  • RBL2 protein, human
  • Retinoblastoma-Like Protein p107
  • Retinoblastoma-Like Protein p130
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27