Cyclooxygenase-2 (cox-2) expression is an independent predictor of prostate cancer recurrence

被引:62
作者
Cohen, Brian L.
Gomez, Pablo
Omori, Yohei
Duncan, Robert C.
Civantos, Francisco
Soloway, Mark S.
Lokeshwar, Vinata B.
Lokeshwar, Bal L.
机构
[1] Univ Miami, Miller Sch Med, Dept Urol, Miami, FL 33101 USA
[2] Univ Miami, Miller Sch Med, Dept Pathol, Miami, FL 33101 USA
[3] Univ Miami, Miller Sch Med, Dept Cell Biol & Anat, Miami, FL 33101 USA
[4] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33101 USA
[5] Univ Miami, Miller Sch Med, Dept Radiat Oncol, Miami, FL 33101 USA
关键词
inflammation; immunohistochemistry; PSA; cancer progression; prognostic indicators; multivariate analysis; tumor markers;
D O I
10.1002/ijc.21749
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Lack of reliable prognostic markers hinders accurate prediction of disease progression in prostate cancer. The inducible proinflammatory enzyme cyclooxygenase-2 (COX-2) is implicated in prostate carcinogenesis, but its role in cancer progression is less clear. We examined whether COX-2 expression evaluated by immunohistochemistry (IHC) in radical prostatectomy (RP) specimens can predict biochemical recurrence. Archival prostate cancer specimens (n = 60) were obtained from patients who underwent RP, but had not received neoadjuvant hormonal therapy. Twenty-three patients had biochemical or clinical recurrence (mean time of recurrence: 38.2 months), and 37 patients were recurrence free (mean follow-up: 95 months). COX-2 expression was determined by IHC, using an anti-COX-2 antibody. Three individuals scored the staining independently, as high- or low-expression. COX-2 was expressed in prostate cancer cells, in adjacent normal glands and in specimens from patients who later progressed. At 62-months follow-up, COX-2 staining predicted progression with 82.4% sensitivity and 81.3% specificity. Sensitivity (86.4%) and specificity (86.7%) improved at >= 100-months follow-up. In univariate analysis, Gleason score, preoperative PSA, extraprostatic extension, margin, seminal vesicle invasion, and high COX-2 expression were significant predictors of biochemical recurrence (p < 0.05). In multivariate analysis, preoperative PSA (hazard ratio/unit PSA change 1.080; p = 0.0036) and COX-2 expression (hazard ratio 16.442; p < 0.0001) were independent prognostic indicators. Patients with PSA > 7 ng/ml and high COX-2 expression had the highest probability of recurrence (Kaplan-Meier analysis). COX-2 expression is an independent predictor of prostate cancer progression following RP and underscores the significance of inflammatory factors in this process. (c) 2006 Wiley-Liss, Inc.
引用
收藏
页码:1082 / 1087
页数:6
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