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 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.
Leoncini
L
L
Institute of Pathologic Anatomy and Histology, University of Sassari, Italy.
Bellan
C
C
Cossu
A
A
Claudio
P P
PP
Lazzi
S
S
Cinti
C
C
Cevenini
G
G
Megha
T
T
Laurini
L
L
Luzi
P
P
Orcioni
G F
GF
Piccioli
M
M
Pileri
S
S
Giardino
C
C
Tosi
P
P
Giordano
A
A
D000368:Aged; D002455:Cell Division; D005260:Female; D006131:Growth Inhibitors / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000502:physiology*; D010750:Phosphoproteins / Q000096:biosynthesis / Q000502:physiology*; D011506:Proteins; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
D006131:Growth Inhibitors; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; C493844:RBL1 protein, human; C493837:RBL2 protein, human; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130