Decreased α-methylacyl CoA racemase expression in localized prostate cancer is associated with an increased rate of biochemical recurrence and cancer-specific death
Decreased α-methylacyl CoA racemase expression in localized prostate cancer is associated with an increased rate of biochemical recurrence and cancer-specific death
复制标题
DOI：
10.1158/1055-9965.epi-04-0801
复制
发表时间：
2005-06-01
影响因子：
3.8
通讯作者：
Johansson, JE
中科院分区：
文献类型：
--
作者：
Rubin, MA;Bismar, TA;Johansson, JE
α-甲基酰辅酶A消旋酶(AMACR)在前列腺癌组织中相对良性前列腺组织中过度表达。AMACR在局限性前列腺癌中表达最高，在转移性前列腺癌中表达降低。在此，我们探讨了AMACR作为侵袭性前列腺癌的生物标记物的应用。应用免疫组织化学方法和图像分析系统检测了204例前列腺癌根治术患者和188例术后随访患者的AMACR蛋白表达。队列的终点是前列腺特异性抗原(PSA)失效的时间(即，Elevation>；0.2 ng/mL)和前列腺癌死亡的时间。使用回归树方法，确定了AMACR蛋白表达的最佳切点，以最好地区分每个队列中的前列腺癌结果。然后使用COX比例风险模型检验AMACR切点对前列腺癌预后的影响，并对临床变量进行调整。AMACR组织低表达与前列腺癌预后恶化相关，与临床变量无关(PSA失败的风险比为3.7P=0.018；前列腺癌死亡的风险比为4.1P=0.0006)。在AMACR低表达和Gleason评分高的患者中，前列腺癌死亡风险是对照组的18倍(P=0.006)。以前列腺癌特异性死亡为终点的AMACR临界点预测PSA失败与Gleason评分、PSA和切缘状态无关。这是第一项表明AMACR表达与前列腺癌进展显著相关的研究，并表明并不是所有的替代终点都可能是确定侵袭性前列腺癌生物标记物的最佳选择。
alpha-Methylacyl CoA racemase (AMACR) is overexpressed in prostate cancer relative to benign prostatic tissue. AMACR expression is highest in localized prostate cancer and decreases in metastatic prostate cancer. Herein, we explored the use of AMACR as a biomarker for aggressive prostate cancer. AMACR protein expression was determined by immunohistochemistry using an image analysis system on two localized prostate cancer cohorts consisting of 204 men treated by radical prostatectomy and 188 men followed expectantly. The end points for the cohorts were time to prostate-specific antigen (PSA) failure (i.e., elevation > 0.2 ng/mL) and time to prostate cancer death in the watchful waiting cohort. Using a regression tree method, optimal AMACR protein expression cutpoints were determined to best differentiate prostate cancer outcome in each of the cohorts separately. Cox proportional hazard models were then employed to examine the effect of the AMACR cutpoint on prostate cancer outcome, and adjusted for clinical variables. Lower AMACR tissue expression was associated with worse prostate cancer outcome, independent of clinical variables (hazard ratio, 3.7 for PSA failure; P = 0.018; hazard ratio, 4.1 for prostate cancer death, P = 0.0006). Among those with both low AMACR expression and high Gleason score, the risk of prostate cancer death was 18-fold higher (P = 0.006). The AMACR cutpoint developed using prostate cancer-specific death as the end point predicted PSA failures independent of Gleason score, PSA, and margin status. This is the first study to show that AMACR expression is significantly associated with prostate cancer progression and suggests that not all surrogate end points may be optimal to define biomarkers of aggressive prostate cancer.