Retinoblastoma-related p107 and pRb2/p130 proteins in malignant lymphomas: distinct mechanisms of cell growth control

Clin Cancer Res. 1999 Dec;5(12):4065-72.

Abstract

pRb/p105, p107, and pRb2/p130 compose the retinoblastoma (RB) family of proteins and regulate cellular growth and differentiation. Because recent functional studies have indicated that the expression of the RB-related proteins p107 and pRb2/p130 are tightly cell cycle regulated, we were interested in investigating their expression along with cellular kinetic characteristics and proliferative features of non-Hodgkin's lymphomas (NHLs). p107 and pRb2/ p130 expression was determined immunohistochemically in biopsy specimens from 83 untreated patients with NHLs of various histiotypes. The expression of these two RB-related proteins was correlated with the mitotic index, apoptotic index, and percentages of Ki-67(+), cyclin A(+), p34(+), and cyclin B(+) cells. The overall survival rate was evaluated according to the Kaplan-Meier method and the log-rank test. We found a positive correlation between the percentages of cells positive for p107 and proliferative features such as mitotic index and percentage of Ki-67(+) and cyclin A(+) cells, whereas such correlation could not be demonstrated for the percentages of pRb2/p130 positive cells. Low immunohistochemical levels of pRb2/p130 detected in untreated patients with NHLs of various histiotypes inversely correlated with a large fraction of cells expressing high levels of p107 and proliferation-associated proteins. Such a pattern of protein expression is normally observed in continuously cycling cells. Interestingly, such cases showed the highest survival percentage (82.5%) after the observation period of 10 years. Thus, down-regulation of the RB-related pRb2/p130 protein could be one of the reasons why these cases display such a high rate of proliferation and why they respond so well to therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Cell Division
  • Female
  • Growth Inhibitors / metabolism
  • Growth Inhibitors / physiology*
  • Humans
  • Immunohistochemistry
  • Lymphoma, Non-Hodgkin / metabolism
  • Lymphoma, Non-Hodgkin / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / physiology*
  • Phosphoproteins / biosynthesis
  • Phosphoproteins / physiology*
  • Proteins*
  • Retinoblastoma-Like Protein p107
  • Retinoblastoma-Like Protein p130
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome

Substances

  • Growth Inhibitors
  • Nuclear Proteins
  • Phosphoproteins
  • Proteins
  • RBL1 protein, human
  • RBL2 protein, human
  • Retinoblastoma-Like Protein p107
  • Retinoblastoma-Like Protein p130