术前p53、bcl-2、CD44和E-钙黏蛋白免疫组化作为根治性前列腺切除术后生化复发的预测指标。

Preoperative p53, bcl-2, CD44 and E-cadherin immunohistochemistry as predictors of biochemical relapse after radical prostatectomy.

作者信息

Brewster S F, Oxley J D, Trivella M, Abbott C D, Gillatt D A

机构信息

Bristol Urological Institute, Department of Cellular Pathology, Southmead Hospital, University of Bristol, United Kingdom.

出版信息

J Urol. 1999 Apr;161(4):1238-43.

PMID:10081877

Abstract

PURPOSE

Since radical prostatectomy is performed to cure prostate cancer, identification of markers enabling preoperative prediction of relapse after radical prostatectomy is essential to counsel and select patients for adjuvant therapy. Aberrant p53, bcl-2, CD44 and E-cadherin immunohistochemistry has been associated with aggressiveness in prostate cancer. We assessed these biomarkers in biopsy and radical prostatectomy specimens as predictors of biochemical relapse.

MATERIALS AND METHODS

A total of 76 patients with untreated clinically localized prostatic adenocarcinoma underwent radical prostatectomy. Preoperative (prostate specific antigen, biopsy Gleason score) and postoperative (pathological stage and margin status) variables, biopsy and radical prostatectomy biomarker immunohistochemistry were correlated with relapse. Univariate and multivariate statistical analyses identified significant predictors.

RESULTS

Of the 76 patients 23 (30%) had relapse (mean followup 38 months). Aberrant p53, bcl-2, CD44 and E-cadherin expression was observed in 64, 12, 85 and 12% of biopsies and 57, 20, 64 and 49% of radical prostatectomy specimens, respectively. Biopsy Gleason 7 to 10 and biopsy p53, respectively, gave the highest positive and negative predictive values for relapse. Relapse occurred in 13% of patients with normal biopsy p53 and in half with aberrant p53. Multivariate analysis revealed Gleason score and p53 to be independent preoperative predictors (p = 0.01 and 0.02, respectively). Estimated risk of relapse was 3.5 times higher in patients with Gleason scores 7 to 10 and 24% higher in those with aberrant p53. Significant postoperative predictors were bcl-2, p53, Gleason score and margin status (p = 0.01, 0.01, 0.04 and 0.01, respectively).

CONCLUSIONS

Aberrant biopsy p53 is associated with a significantly worse outcome after radical prostatectomy than normal p53, highlighting a potential clinical role for p53. Postoperative p53 and bcl-2 were significant predictors of outcome after radical prostatectomy.

摘要

目的

由于根治性前列腺切除术旨在治愈前列腺癌，因此识别能够术前预测根治性前列腺切除术后复发的标志物对于为辅助治疗咨询和选择患者至关重要。异常的p53、bcl-2、CD44和E-钙黏蛋白免疫组化与前列腺癌的侵袭性相关。我们评估了活检和根治性前列腺切除标本中的这些生物标志物作为生化复发的预测指标。

材料与方法

共有76例未经治疗的临床局限性前列腺腺癌患者接受了根治性前列腺切除术。术前（前列腺特异性抗原、活检Gleason评分）和术后（病理分期和切缘状态）变量、活检和根治性前列腺切除标本生物标志物免疫组化与复发相关。单因素和多因素统计分析确定了显著的预测指标。

结果

76例患者中23例（30%）复发（平均随访38个月）。活检中异常p53、bcl-2、CD44和E-钙黏蛋白表达分别见于64%、12%、85%和12%的患者，根治性前列腺切除标本中分别为57%、20%、64%和49%。活检Gleason评分7至10分和活检p53分别对复发给出了最高的阳性和阴性预测值。活检p53正常的患者中有13%复发，p53异常的患者中有一半复发。多因素分析显示Gleason评分和p53是独立的术前预测指标（分别为p = 0.01和0.02）。Gleason评分7至10分的患者复发风险估计高3.5倍，p53异常的患者高24%。显著的术后预测指标是bcl-2、p53、Gleason评分和切缘状态（分别为p = 0.01、0.01、0.04和0.01）。