p53、bcl-2和KI-67（MIB-1）的蛋白表达作为手术治疗的临床局限性前列腺癌患者的预后生物标志物。

Protein expression of p53, bcl-2, and KI-67 (MIB-1) as prognostic biomarkers in patients with surgically treated, clinically localized prostate cancer.

作者信息

Moul J W, Bettencourt M C, Sesterhenn I A, Mostofi F K, McLeod D G, Srivastava S, Bauer J J

机构信息

Department of Surgery, Walter Reed Army Medical Center, Washington, D.C., USA.

出版信息

Surgery. 1996 Aug;120(2):159-66; discussion 166-7. doi: 10.1016/s0039-6060(96)80283-2.

DOI:10.1016/s0039-6060(96)80283-2

PMID:8751578

Abstract

BACKGROUND

Protein expression in the primary tumor of the tumor suppressor gene p53 and the proto-oncogene bcl-2 have been shown to be prognostic biomarkers of cancer recurrence after radical prostatectomy in patients with clinically localized prostate cancer. Cancer cell proliferation as measured by immunohistochemical markers such as the MIB-1 antibody for Ki-67 has recently been suggested to be of prognostic value in prostate cancer. The goal of this study was to determine the clinical use of p53, Ki-67 (MIB-1), and bcl-2 immunohistochemical protein expression in the primary tumor as combined predictors of disease progression after radical prostatectomy (RP).

METHODS

Protein expressions of p53, Ki-67, and bcl-2 were evaluated in archival paraffin-embedded RP specimens from 162 patients monitored from 1 to 10 years (mean, 4.5 years) and correlated to stage, grade, race, and serologic (prostate-specific antigen) recurrence after operation.

RESULTS

Expression was detected in 112 (69.1%), 44 (27.2%), and 62 (38.3%) of 162 patients for p53 (1+ or greater), bcl-2 (1+ or greater), and Ki-67 (2+ or greater), respectively. Biomarker expressions were not correlated to age and race; however, all increased with increasing stage and grade. The degree of expression by percentage of malignant cells staining correlated to recurrence for p53 and Ki-67 but not for bcl-2. All three markers were correlated to raw and Kaplan-Meier recurrence by means of univariate analysis with recurrence estimates at 6 years of 60.7% versus 24.2%, 84.2% versus 38.6%, and 72.4% versus 30.6% comparing positive versus negative expression of p53, bcl-2, and Ki-67, respectively. p53 and bcl-2 remained as independent prognostic markers by Cox multivariate regression analysis. Although Ki-67 did not remain an independent marker, it added prognostic use in certain subsets of patients.

CONCLUSIONS

p53, bcl-2, and Ki-67 (MIB-1) appear to be important biomarkers to predict recurrence in patients with clinically localized prostate cancer after RP, and all three biomarkers deserve further study.

摘要

背景

肿瘤抑制基因p53和原癌基因bcl-2在原发性肿瘤中的蛋白表达已被证明是临床局限性前列腺癌患者根治性前列腺切除术后癌症复发的预后生物标志物。最近有人提出，通过免疫组化标志物（如用于Ki-67的MIB-1抗体）测量的癌细胞增殖在前列腺癌中具有预后价值。本研究的目的是确定原发性肿瘤中p53、Ki-67（MIB-1）和bcl-2免疫组化蛋白表达作为根治性前列腺切除术（RP）后疾病进展的联合预测指标的临床应用价值。

方法

对162例患者的存档石蜡包埋RP标本进行p53、Ki-67和bcl-2蛋白表达评估，这些患者的随访时间为1至10年（平均4.5年），并将其与术后分期、分级、种族和血清学（前列腺特异性抗原）复发情况进行关联分析。

结果

在162例患者中，分别有112例（69.1%）、44例（27.2%）和62例（38.3%）检测到p53（1+或更高）、bcl-2（1+或更高）和Ki-67（2+或更高）的表达。生物标志物表达与年龄和种族无关；然而，所有标志物的表达均随分期和分级的增加而升高。p53和Ki-67的恶性细胞染色百分比表达程度与复发相关，而bcl-2则不然。通过单因素分析，所有这三种标志物均与原始复发率和Kaplan-Meier复发率相关，p53、bcl-2和Ki-67阳性与阴性表达的6年复发估计值分别为60.7%对24.2%、84.2%对38.6%和72.4%对30.6%。通过Cox多因素回归分析，p53和bcl-2仍然是独立的预后标志物。虽然Ki-67不是独立标志物，但它在某些患者亚组中增加了预后价值。