Abstract
Lack of reliable biomarkers limits accurate prediction of prostate-specific antigen biochemical recurrence (disease progression) in prostate cancer. The two inflammatory chemokines, osteopontin and interleukin-8 (IL-8), are associated with tumor angiogenesis and metastasis. We investigated whether osteopontin and IL-8 expression in prostate cancer correlates with disease progression. Archival prostatectomy specimens (n = 103) were obtained from patients with minimum 72-month follow-up. Osteopontin and IL-8 expression was evaluated by immunohistochemistry and graded for intensity and the area. Association of osteopontin and IL-8 staining with biochemical recurrence was evaluated by univariate and multivariate models. In tumor cells, osteopontin and IL-8 staining was higher in the recurred group (203.2 +/- 78.4; 181.1 +/- 89.3) than in the nonrecurred group (122.7 +/- 76.6; 96.4 +/- 85.6; P < 0.001). Higher osteopontin and IL-8 staining was also observed in benign areas adjacent to tumor in the recurred group, than in nonrecurred group. In univariate analysis, except age, all preoperative and postoperative variables and osteopontin and IL-8 staining scores were significantly associated with biochemical recurrence (P < 0.05). In multivariate analysis, margin status and osteopontin staining independently associated with biochemical recurrence within 72 months. Osteopontin, either alone or with IL-8 and seminal vesicle invasion, was a significant variable in predicting biochemical recurrence within 24 months. Osteopontin and IL-8 staining predicted recurrence with high sensitivity (75.5%; 73.6%) and specificity (76%; 70.6%). In prostatectomy specimens, osteopontin expression is independently associated with biochemical recurrence. Both osteopontin and IL-8 may be predictors of early disease progression.
MeSH Terms
Biomarkers, Tumor/metabolism
Disease Progression
Gene Expression Regulation, Neoplastic
Humans
Interleukin-8/biosynthesis,metabolism
Male
Models, Statistical
Multivariate Analysis
Neovascularization, Pathologic
Osteopontin/biosynthesis
Prostatectomy
Prostatic Neoplasms/metabolism,pathology,surgery
Recurrence
Time Factors
Treatment Outcome
Chemicals
Biomarkers, Tumor
Interleukin-8
Osteopontin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Caruso Daniel J
Department of Urology, Miller School of Medicine, University of Miami, Miami, FL 33101, USA.
Carmack Adrienne J K
Lokeshwar Vinata B
Duncan Robert C
Soloway Mark S
Lokeshwar Bal L
References (26)
26 references, click to expand
-
Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the American Urological Association Prostate Guidelines for Localized Prostate Cancer Update Panel report and recommendations for a standard in the reporting of surgical outcomes.
J Urol. 2007 Feb;177(2):540-5
PMID: 17222629
-
Osteopontin: a novel inflammatory mediator of cardiovascular disease.
Front Biosci. 2007 Jan 01;12:214-21
PMID: 17127294
-
Interleukin-8 is a molecular determinant of androgen independence and progression in prostate cancer.
Cancer Res. 2007 Jul 15;67(14):6854-62
PMID: 17638896
-
Genetic polymorphisms of interleukin-1B (IL-1B), IL-6, IL-8, and IL-10 and risk of prostate cancer.
Cancer Res. 2006 Apr 15;66(8):4525-30
PMID: 16618781
-
Survival probabilities (the Kaplan-Meier method).
BMJ. 1998 Dec 5;317(7172):1572
PMID: 9836663
-
Osteopontin: a bridge between bone and the immune system.
J Clin Invest. 2003 Jul;112(2):147-9
PMID: 12865402
-
Cyclooxygenase-2 (COX-2) expression is an independent predictor of prostate cancer recurrence.
Int J Cancer. 2006 Sep 1;119(5):1082-7
PMID: 16557596
-
Bladder tumor markers beyond cytology: International Consensus Panel on bladder tumor markers.
Urology. 2005 Dec;66(6 Suppl 1):35-63
PMID: 16399415
-
Prognostic factors in prostate cancer.
Recent Results Cancer Res. 2007;175:25-32
PMID: 17432552
-
Expression of interleukin-8 correlates with angiogenesis, tumorigenicity, and metastasis of human prostate cancer cells implanted orthotopically in nude mice.
Neoplasia. 2001 Jan-Feb;3(1):33-42
PMID: 11326314
-
Osteopontin: role in cell signaling and cancer progression.
Trends Cell Biol. 2006 Feb;16(2):79-87
PMID: 16406521
-
Osteopontin.
Crit Rev Oral Biol Med. 2000;11(3):279-303
PMID: 11021631
-
Prognostic significance of osteopontin expression in human prostate cancer.
Int J Cancer. 2006 May 1;118(9):2255-61
PMID: 16331611
-
Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer.
Cancer Res. 2002 Jun 15;62(12):3417-27
PMID: 12067984
-
Functional genomic analysis in arthritis-affected cartilage: yin-yang regulation of inflammatory mediators by alpha 5 beta 1 and alpha V beta 3 integrins.
J Immunol. 2000 Mar 1;164(5):2684-91
PMID: 10679109
-
Biochemical recurrence after localized treatment.
Urol Clin North Am. 2006 May;33(2):147-59, v
PMID: 16631453
-
Biochemical staging of prostate cancer.
Urol Clin North Am. 2003 May;30(2):263-77
PMID: 12735503
-
Genetic variation in interleukin 8 and its receptor genes and its influence on the risk and prognosis of prostate cancer among Finnish men in a large cancer prevention trial.
Eur J Cancer Prev. 2006 Jun;15(3):249-53
PMID: 16679868
-
Increased expression of osteopontin contributes to the progression of prostate cancer.
Cancer Res. 2006 Jan 15;66(2):883-8
PMID: 16424021
-
Elevated serum bone sialoprotein and osteopontin in colon, breast, prostate, and lung cancer.
Clin Cancer Res. 2001 Dec;7(12):4060-6
PMID: 11751502
-
Expression of interleukin-8 gene in radical prostatectomy specimens is associated with advanced pathologic stage.
Prostate. 2005 Jun 15;64(1):40-9
PMID: 15651067
-
Adenocarcinoma of the prostate: epidemiological trends, screening, diagnosis, and surgical management of localized disease.
Mayo Clin Proc. 2005 Jul;80(7):899-907
PMID: 16007895
-
Conference report and review: current status of biomarkers potentially associated with prostate cancer outcomes.
J Urol. 2007 Apr;177(4):1229-37
PMID: 17382696
-
What might a stromal response mean to prostate cancer progression?
Cancer Metastasis Rev. 1998-1999;17(4):411-9
PMID: 10453285
-
Molecular prostate cancer pathology: current issues and achievements.
Scand J Urol Nephrol Suppl. 2005 May;(216):82-93
PMID: 16019760
-
Serum interleukin-8 is elevated in men with prostate cancer and bone metastases.
Technol Cancer Res Treat. 2004 Oct;3(5):411
PMID: 15453805