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

Lorenzo Leoncini, Cristiana Bellan, Antonio Cossu, Pier Paolo Claudio, Stefano Lazzi, Caterina Cinti, Gabriele Cevenini, Tiziana Megha, Lorella Laurini, Pietro Luzi, Giulio Fraternali Orcioni, Milena Piccioli, Stefano Pileri, Costantino Giardino, Piero Tosi, Antonio Giordano

Research output: Contribution to journalArticle

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(-t-) 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.

Original languageEnglish
Pages (from-to)4065-4072
Number of pages8
JournalClinical Cancer Research
Volume5
Issue number12
Publication statusPublished - Dec 1999

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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  • Cite this

    Leoncini, L., Bellan, C., Cossu, A., Claudio, P. P., Lazzi, S., Cinti, C., Cevenini, G., Megha, T., Laurini, L., Luzi, P., Orcioni, G. F., Piccioli, M., Pileri, S., Giardino, C., Tosi, P., & Giordano, A. (1999). Retinoblastoma-related p107 and pRb2/p130 proteins in malignant lymphomas: Distinct mechanisms of cell growth control. Clinical Cancer Research, 5(12), 4065-4072.