This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Claudio, P. P. Articles by Cardi, G. Search for Related Content PubMed PubMed Citation Articles by Claudio, P. P. Articles by Cardi, G.

Expression of Cell-Cycle-regulated Proteins pRb2/p130, p107, p27^kip1, p53, mdm-2, and Ki-67 (MIB-1) in Prostatic Gland Adenocarcinoma¹

Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, Pennsylvania [P. P. C., A. Z., A. B., G. R., A. G.]; Department of Pathology, Thomas Jefferson University, Philadelphia, Pennsylvania [P.P.C., A.Z., A.B., G.R., A.G.]; Dipartimento di Scienze Odontostomatologiche e Maxillo-Facciali, Università degli Studi di Napoli "Federico II," Italy [P. P. C.]; Department of Pathology, M.C.P. Hahnemann University, Philadelphia, Pennsylvania [F. U. G.]; Division of Urology, Istituto dei Tumori di Napoli, "Fondazione Senatore Pascale," Naples, Italy [L. C.]; University of California, Irvine School of Medicine, Irvine, California [G. A.]; Istituto di Embriologia, Università di Bologna, Italy [A. F.]; Department of Pathology, Seconda Università degli Studi di Napoli, Italy [G. G. G.]; and Department of Urology [D. E. M.], and Division of Medical Oncology [G. C.], Thomas Jefferson University, Philadelphia, Pennsylvania

Purpose: The quest for prognostic molecular markers in prostatic carcinoma is still in progress. Many proteins have already been screened by immunohistochemistry with the aim to find the most reliable indicator of progressive disease. In this study, we evaluated the expression of pRb2/p130, p107, p27^kip1, p53, mdm-2, and Ki-67 (MIB-1) by immunohistochemistry in 24 prostate carcinomas compared with the paired expression of normal prostates.

Experimental Design: Expression of the different proteins in normal and pathological specimens was evaluated by the Wilcoxon test. A matrix of correlation (Spearman coefficient) was used to evaluate the possible association in expression among the different proteins. Logistic regression analysis was used to test the multivariable prognostic value of the levels of protein expression for the probability of disease development.

Results: p53 and Ki-67 (MIB-1) showed a higher expression in cancer than in normal tissue (P = 0.006 and <0.001, respectively). pRb2/p130, p107, and p27^kip1 showed an overall lower expression in cancer, but the difference between cytoplasmic and nuclear expression was always higher for cancer (Ps, from <0.001 to 0.016). mdm-2 expression was lower in cancer, but the difference between cytoplasmic and nuclear expression was not significant (P = 0.571) when compared with that in normal tissue. A positive correlation between p27 and pRb2/p130 levels expressed, in normal and cancer counterparts in the same sample, as the difference between cytoplasmic and nuclear protein concentrations (P = 0.045) was found. Additionally, p107 expression showed an inverse correlation with Ki-67 (MIB-1) expression in the most aggressive tumors (P = 0.046). Logistic regression output showed that Ki-67 (MIB-1) and pRb2/p130 (expressed as differences between cytoplasmic and nuclear concentrations) were the variables associated with a higher risk of cancer. The highest value was reported for Ki-67 (MIB-1) (odds ratio, 2.11), followed by pRb2/p130 (odds ratio, 1.01). pRb2/p130 alone was associated with a sensitivity (rate of cases having a posterior probability of disease 0.5) of 61% with a false positive rate of 22%. Ki-67 (MIB-1) alone yielded a sensitivity of 69% and a false positive rate of 14%. The combined model (Ki-67 + pRb2/p130) yielded a sensitivity of 83% with a false positive rate of 17%. Interestingly, one specimen in which we also found a high-grade prostatic intraepithelial neoplasia showed the progressive loss of pRb2/p130 from normal prostatic cells to prostatic intraepithelial neoplasia cells, suggesting that in prostatic cancer, lack of expression of the tumor suppressor gene pRb2/p130 could be involved in the progression of the disease, from an early stage.

Conclusions: This study showed that all of the proteins but mdm-2 were expressed at a different rate in normal and pathological prostate specimens. Multivariate analysis showed that pRb2/p130 and p107 may be involved in the pathogenesis and progression of prostate cancers, and that the expression of the retinoblastoma-related protein pRb2/p130 along with Ki-67 (MIB-1), expressed as differences between cytoplasmic and nuclear concentrations, could be considered new parameters to be evaluated in discriminating patients at a higher risk for prostate cancer.

This article has been cited by other articles:

				A. Psyrri, A. Bamias, Z. Yu, P. M. Weinberger, M. Kassar, S. Markakis, D. Kowalski, E. Efstathiou, R. L. Camp, D. L. Rimm, et al. Subcellular Localization and Protein Levels of Cyclin-Dependent Kinase Inhibitor p27 Independently Predict for Survival in Epithelial Ovarian Cancer Clin. Cancer Res., December 1, 2005; 11(23): 8384 - 8390. [Abstract] [Full Text] [PDF]

				R. Hill, Y. Song, R. D. Cardiff, and T. Van Dyke Heterogeneous Tumor Evolution Initiated by Loss of pRb Function in a Preclinical Prostate Cancer Model Cancer Res., November 15, 2005; 65(22): 10243 - 10254. [Abstract] [Full Text] [PDF]

				G. Russo, A. Zamparelli, C. M. Howard, C. Minimo, C. Bellan, G. Carillo, L. Califano, L. Leoncini, A. Giordano, and P. P. Claudio Expression of Cell Cycle-Regulated Proteins pRB2/p130, p107, E2F4, p27, and pCNA in Salivary Gland Tumors: Prognostic and Diagnostic Implications Clin. Cancer Res., May 1, 2005; 11(9): 3265 - 3273. [Abstract] [Full Text] [PDF]

				G. Gannot, J. W. Gillespie, R. F. Chuaqui, M. A. Tangrea, W. M. Linehan, and M. R. Emmert-Buck Histomathematical Analysis of Clinical Specimens: Challenges and Progress J. Histochem. Cytochem., February 1, 2005; 53(2): 177 - 185. [Abstract] [Full Text] [PDF]

				T. Tonini, C. Gabellini, L. Bagella, G. D'Andrilli, V. Masciullo, G. Romano, G. Scambia, G. Zupi, and A. Giordano pRb2/p130 Decreases Sensitivity to Apoptosis Induced by Camptothecin and Doxorubicin but not by Taxol Clin. Cancer Res., December 1, 2004; 10(23): 8085 - 8093. [Abstract] [Full Text] [PDF]

				L. A. Maddison, B. W. Sutherland, R. J. Barrios, and N. M. Greenberg Conditional Deletion of Rb Causes Early Stage Prostate Cancer Cancer Res., September 1, 2004; 64(17): 6018 - 6025. [Abstract] [Full Text] [PDF]

				H. Huynh Overexpression of tumour suppressor retinoblastoma 2 protein (pRb2/p130) in hepatocellular carcinoma Carcinogenesis, August 1, 2004; 25(8): 1485 - 1494. [Abstract] [Full Text] [PDF]

				G. D'Andrilli, V. Masciullo, L. Bagella, T. Tonini, C. Minimo, G. F. Zannoni, R. L. Giuntoli II, J. A. Carlson Jr., D. R. Soprano, K. J. Soprano, et al. Frequent Loss of pRb2/p130 in Human Ovarian Carcinoma Clin. Cancer Res., May 1, 2004; 10(9): 3098 - 3103. [Abstract] [Full Text] [PDF]

				L.-Q. Qiu, R. Sinniah, and S. I-Hong Hsu Downregulation of Bcl-2 by Podocytes Is Associated with Progressive Glomerular Injury and Clinical Indices of Poor Renal Prognosis in Human IgA Nephropathy J. Am. Soc. Nephrol., January 1, 2004; 15(1): 79 - 90. [Abstract] [Full Text] [PDF]

				J. T. Posey, M. S. Soloway, S. Ekici, M. Sofer, F. Civantos, R. C. Duncan, and V. B. Lokeshwar Evaluation of the Prognostic Potential of Hyaluronic Acid and Hyaluronidase (HYAL1) for Prostate Cancer Cancer Res., May 15, 2003; 63(10): 2638 - 2644. [Abstract] [Full Text] [PDF]