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Retinoblastoma-related p107 and pRb2/p130 Proteins in Malignant Lymphomas: Distinct Mechanisms of Cell Growth Control¹

Institute of Pathologic Anatomy and Histology, University of Sassari, Sassari, Italy [L. L., A. C.]; Institute of Pathologic Anatomy and Histology [C. B., S. L., T. M., L. L., P. L., P. T.] and Institute of Thoracic and Cardiovascular Surgery and Biomedical Technology [G. C.], University of Siena, Siena, Italy; Departments of Pathology, Anatomy, and Cell Biology, Jefferson Medical College, and Sbarro Institute for Cancer Research and Molecular Medicine, Philadelphia, Pennsylvania 19107 [P. P. C., A. G.]; Department of Scienze Odontostomatologiche e Maxillo-Facciali, Universitá degli Studi di Napoli "Federico II," Napoli, Italy [P. P. C., C. G.]; Institute of Normal and Pathologic Cytomorphology, Consiglio Nazionale delle Ricerche, Bologna, Italy [C. C.]; and Institute of Hematology, "L.&A. Seragnoli," Hemolymphopathology Unit, University of Bologna, Bologna, Italy [G. F. O., M. P., S. P.]

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.

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