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

pRb/p105, p107, and pRb2/p130 compose the retinoblastoma (RB) family of pro teins and regulate cellular growth and differentiation, Because recent func tional studies have indicated that the expression of the RE-related protein s p107 and pRb2/p130 are tightly cell cycle regulated, we were interested i n investigating their expression along with cellular kinetic characteristic s and proliferative features of non-Hodgkin's lymphomas (NHLs). p107 and pR b2/p130 expression was determined immunohistochemically in biopsy specimens from 83 untreated patients,vith NHLs of various histiotypes. The expressio n of these two RE-related proteins was correlated with the mitotic index, a poptotic index, and percentages of Ki-67(+), cyclin A(+), p34(+), and cycli n B(+) cells. The overall survival rate was evaluated according to the Kapl an-Meier method and the log-rank test. We found a positive correlation betw een the percentages of cells positive for p107 and proliferative features s uch as mitotic index and percentage of Ki-67(+) and cyclin A(+) cells, wher eas such correlation could not be demonstrated for the percentages of pRb2/ p130 positive cells. Low immunohistochemical levels of pRb2/p130 detected i n untreated patients with NHLs of various histiotypes inversely correlated with a large fraction of cells expressing high levels of p107 and prolifera tion-associated proteins. Such a pattern of protein expression is normally observed in continuously cycling cells, Interestingly, such cases showed th e highest survival percentage (82.5%) after the observation period of 10 ye ars. Thus, down-regulation of the RE-related pRb2/p130 protein could be one of the reasons why these cases display such a high rate of proliferation a nd why they respond so well to therapy.