[en] BACKGROUND: Bone sialoprotein (BSP), a bone matrix protein, was recently found to be expressed ectopically in breast cancer and to have a statistically significant association with poor prognosis and the development of bone metastases in that disease. These data prompted us to investigate whether BSP might also be expressed in human prostate cancer, which often metastasizes to bone, and be predictive for progression risk. METHODS: Tissue sections from 180 patients who had undergone a radical prostatectomy for localized prostate cancer were analyzed immunohistochemically for BSP expression. Biochemical progression was defined as an increasing serum prostate-specific antigen level of 0.5 ng/mL or more. Statistical analysis was used to assess associations between pathologic findings and level of BSP expression, and a Cox proportional hazards model was used to determine which clinical and histologic parameters, including stage, Gleason score, and BSP expression (immunostaining intensity and extent), were independently associated with biochemical progression. All P values were two-sided. RESULTS: Most of the prostate cancer lesions examined (78.9%) expressed detectable levels of BSP, compared with no or low expression in the adjacent normal glandular tissue. A statistically significant association was found between BSP expression and biochemical progression in both univariate and multivariate analyses. After a follow-up interval of 3 years, the biochemical relapse rate was 36.7% (95% confidence interval [CI] = 23.4%-47.7%) in patients whose tumors expressed high levels of BSP compared with 12.1% (95% CI = 2.3%-20.8%) in patients whose tumors expressed no or a low detectable level of the protein (logrank test, P = .0014). BSP expression status could identify those patients at higher risk of biochemical progression (logrank test, P<.05) among patients with moderately differentiated tumors or with pathologically confined tumors. CONCLUSIONS: To our knowledge, this study is the first to demonstrate BSP expression in human prostate cancer and to highlight the protein's statistically significant prognostic value in patients with clinically confined prostate adenocarcinomas.
Disciplines :
Urology & nephrology
Author, co-author :
Waltregny, David ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Labo de recherche sur les métastases
Bellahcene, Akeila ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Labo de recherche sur les métastases
Van Riet, Ivan
Fisher, Larry W
Young, Marianne
Fernandez, Pedro
Dewé, Walthère ; Université de Liège - ULiège > Analyse des médicaments
de Leval, Jean ; Université de Liège - ULiège > Département des sciences cliniques > Urologie
Castronovo, Vincenzo ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
Language :
English
Title :
Prognostic Value of Bone Sialoprotein Expression in Clinically Localized Human Prostate Cancer
Batson OV. The function of the vertebral veins and their role in the spread of metastases. Ann Surg 1940; 112:138-49.
Zetter BR. The cellular basis of site-specific tumor metastasis. N Engl J Med 1990;332: 605-12.
Zetter BR, Chackal-Roy M, Smith R. The cellular basis for prostate cancer metastasis. In: Karr JP, Yamanaka H, editors. Prostate cancer and bone metastasis. New York: Plenum Press, 1992:39-43.
Paget S. The distribution of secondary growths in cancer of the breast. Lancet 1889;1:571-3.
Haq M, Goltzman D, Tremblay G, Brodt P. Rat prostate adenocarcinoma cells disseminate to bone and adhere preferentially to bone marrow-derived endothelial cells. Cancer Res 1992;52:4613-9.
Bellahcene A, Merville MP, Castronovo V. Expression of bone sialoprotein, a bone matrix protein, in human breast cancer. Cancer Res 1994;54:2823-6.
Hunter GK, Goldberg HA. Modulation of crystal formation by bone phosphoproteins: role of glutamic acid-rich sequences in the nucleation of hydroxyapatite by bone sialoprotein. Biochem J 1994;302(Pt 1):175-9.
Fisher LW, McBride OW, Termine JD, Young MF. Human bone sialoprotein. Deduced protein sequence and chromosomal localization. J Biol Chem 1990;265:2347-51.
Chen JK, Shapiro HS, Wrana JL, Reimers S, Heersche JN, Sodek J. Localization of bone sialoprotein (BSP) expression to sites of mineralized tissue formation in fetal rat tissues by in situ hybridization. Matrix 1991;11:133-43.
Gehron Robey P. Bone matrix proteoglycans and glycoproteins. In: Bilezikian J, Raisz L, Rodan G, editors. Principles of bone biology. New York: Academic Press, 1996:155-67.
Bianco P, Fisher L, Young M. Expression of bone sialoprotein in human developing bone as revealed by immunostaining and in situ hybridization. J Bone Min Res 1989;4(Suppl): S246.
Bianco P, Fisher LW, Young MF, Termine JD, Gehron Robey P. Expression of bone sialoprotein (BSP) in developing human tissues. Calcif Tissue Int 1991;49:421-6.
Fisher LW, Whitson SW, Avioli LV, Termine JD. Matrix sialoprotein of developing bone. J Biol Chem 1983;258:12723-7.
Bellahcene A, Maloujahmoum N, Fisher LW, Pastorino H, Tagliabue E, Menard S, et al. Expression of bone sialoprotein in human lung cancer. Calcif Tissue Int 1997;61:183-8.
Bellahcene A, Van Riet I, Antoine N, Van Camp B, Castronovo V. Expression of a bone matrix protein in myeloma cell lines [abstract]. Proc Annu Am Assoc Cancer Res 1996;A618: 37.
Bellahcene A, Kroll M, Liebens F, Castronovo V. Bone sialoprotein expression in primary human breast cancer is associated with bone metastases development. J Bone Miner Res 1996; 11:665-70.
Bellahcene A, Menard S, Bufalino R, Moreau L, Castronovo V. Expression of bone sialoprotein in primary human breast cancer is associated with poor survival. Int J Cancer 1996;69: 350-3.
Schroder FH, Hermanek P, Denis L, Fair WR, Gospodarowicz MK, Pavone-Macaluso M. The TNM classification of prostate cancer. Prostate Suppl 1992;4:129-38.
Gleason DF, Mellinger GT. Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J Urol 1974;111:58-64.
Mintz KP, Grzesik WJ, Midura RJ, Robey PG, Termine JD, Fisher LW. Purification and fragmentation of nondenatured bone sialoprotein: evidence for a cryptic, RGD-resistant cell attachment domain. J Bone Miner Res 1993;8: 985-95.
Sjogren S, Inganas M, Norberg T, Lindgren A, Nordgren H, Holmberg L, et al. The p53 gene in breast cancer: prognostic value of complementary DNA sequencing versus immunohistochemistry. J Natl Cancer Inst 1996;88: 173-82.
Wheeler TM, Lebovitz RM. Fresh tissue harvest for research from prostatectomy specimens. Prostate 1994;25:274-9.
MacPhee D, Belli veau D, Naus CC, Kidder GM. Detection of nuclear and cytoplasmic mRNAs utilizing digoxigenin-labeled probes for in situ hybridization. Biochemica 1995;1: 22-4.
Watanabe K, Yamada H, Yamagucji Y. K-glypican: a novel GPI-anchored heparan sulfate proteoglycan that is highly expressed in developing brain and kidney. J Cell Biol 1995; 130:1207-18.
Angata K, Nakayama J, Fredette B, Chong K, Ranscht B, Fukuda M. Human STX polysialyltransferase forms the embryonic form of the neural cell adhesion molecule. Tissue-specific expression, neurite outgrowth, and chromosomal localization in comparison with another polysialyltransferase, PST. J Biol Chem 1997; 272:7182-90.
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-81.
Cox DR. Regression models and life-tables. J Roy Stat Soc 1972;34:187.
Catalona WJ, Smith DS, Ratliff TL, Basler JW. Detection of organ-confined prostate cancer is increased through prostate-specific antigen-based screening. JAMA 1993;270:948-54.
Smith DS, Catalona WJ. The nature of prostate cancer detected through prostate specific antigen based screening. J Urol 1994; 152(Pt 2): 1732-6.
Lerner SE, Seay TM, Blute ML, Bergstralh EJ, Barren D, Zincke H. Prostate specific antigen detected prostate cancer (clinical stage T1c): an interim analysis. J Urol 1996;155:821-6.
Oesterling JE, Suman VJ, Zincke H, Bostwick DG. PSA-detected (clinical stage T1c or B0) prostate cancer. Pathologically significant tumors. Urol Clin N Am 1993;20:687-93.
Epstein JI, Walsh PC, Carmichael M, Brendler CB. Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA 1994;271:368-74.
Stamey TA, Freiha FS, McNeal JE, Redwine EA, Whittemore AS, Schmid HP. Localized prostate cancer. Relationship of tumor volume to clinical significance for treatment of prostate cancer. Cancer 1993;71:993-8.
Grayhack JT, Grayhack JJ. Clinical dilemmas and problems in assessing prostatic metastasis to bone: the scientific challenge. In: Karr JP, Yamanaka H, editors. Prostate cancer and bone metastasis. New York: Plenum Press, 1992: 1-5.
Jacobs SC. Spread of prostatic cancer to bone. Urology 1983;21:337-44.
Franks LM. The spread of prostatic cancer. J Pathol Bacteriol 1956;72:603-11.
Mintz ER, Smith GG. Autopsy findings in 100 cases of prostatic cancer. N Engl J Med 1934; 211:479-87.
Bernstein LR, Liotta LA. Molecular mediators of interactions with extracellular matrix components in metastasis and angiogenesis. Curr Opin Oncol 1994;6:106-13.
van der Pluijm G, Vloedgraven H, Papapoulos S, Gehron Robey P, Lowik CW. Integrins mediate adhesion of breast cancer cells to various stages of developing bone. J Bone Miner Res 1994;9(Suppl):S421.
Pignatelli M, Cardillo MR, Hanby A, Stamp GW. Integrins and their accessory adhesion molecules in mammary carcinomas: loss of polarization in poorly differentiated tumors. Hum Pathol 1992;23:1159-66.
Koukoulis GK, Virtanen I, Korhonen M, Laitinen L, Quaranta V, Gould VE. Immunohistochemical localization of integrins in the normal, hyperplastic, and neoplastic breast. Correlations with their functions as receptors and cell adhesion molecules. Am J Pathol 1991;139:787-99.
van der Pluijm G, Kerr J, Lowik C, Gehron-Robey P. β1 and β3 integrin subunits are involved in adhesion of breast cancer cells to extracellular bone matrix. J Bone Miner Res 1993;8 (Suppl):S136.
Kitazawa S, Maeda S. Development of skeletal metastases. Clin Orthop 1995;312:45-50.
van der Pluijm G, Vloedgraven HJ, Ivanov B, Robey FA, Grzesik WJ, Robey PG, et al. Bone sialoprotein peptides are potent inhibitors of breast cancer cell adhesion to bone. Cancer Res 1996;56:1948-55.
McNeal JE, Villers AA, Redwine EA, Freiha FS, Stamey TA. Histologic differentiation, cancer volume, and pelvic lymph node metastasis in adenocarcinoma of the prostate. Cancer 1990;66:1225-33.
Kramer SA, Spahr J, Brendler CB, Glenn JF, Paulson DF. Experience with Gleason's histopathologic grading in prostatic cancer. J Urol 1980;124:223-5.
Walsh PC, Partin AW, Epstein JI. Cancer control and quality of life following anatomical radical retropubic prostatectomy: results at 10 years. J Urol 1994;152(Pt 2):1831-6.
Trapasso JG, deKernion JB, Smith RB, Dorey F. The incidence and significance of detectable levels of serum prostate specific antigen after radical prostatectomy. J Urol 1994;152(Pt 2): 1821-5.
Stein A, deKernion JB, Smith RB, Dorey F, Patel H. Prostate specific antigen levels after radical prostatectomy in patients with organ confined and locally extensive prostate cancer. J Urol 1992;147(Pt 2):942-6.
Ohori M, Wheeler TM, Kattan MW, Goto Y, Scardino PT. Prognostic significance of positive surgical margins in radical prostatectomy specimens. J Urol 1995;154:1818-24.
Walsh PC, Lepor H. The role of radical prostatectomy in the management of prostatic cancer. Cancer 1987;60(3 Suppl):526-37.
Epstein JI, Pizov G, Walsh PC. Correlation of pathologic findings with progression following radical retropubic prostatectomy. Cancer 1993; 71:3582-93.
Partin AW, Pound CR, Clemens JQ, Epstein JI, Walsh PC. Serum PSA after anatomic radical prostatectomy. The Johns Hopkins experience after 10 years. Urol Clin N Am 1993;20: 713-25.
Watregny D, de Leval L, Menard S, de Leval J, Castronovo V. Independent prognostic value of the 67-kd laminin receptor in human prostate cancer. J Natl Cancer Inst 1997;89:1224-7.