Theodorescu D, Broder S R, Boyd J C, Mills S E, Frierson H F
Department of Urology, University of Virginia Health Sciences Center, Charlottesville, USA.
J Urol. 1997 Jul;158(1):131-7. doi: 10.1097/00005392-199707000-00040.
The accumulation of p53 and bcl-2 gene products as well as the loss of the retinoblastoma (Rb) gene product have been associated with prostate cancer progression. We assessed whether the levels of immunoreactivity for p53, Rb and bcl-2 are better long-term predictors of disease specific survival than conventional pathological parameters of the primary tumor, such as Gleason score, capsular penetration, seminal vesicle invasion and percent tumor in the specimen, in patients with clinically localized prostate cancer treated with radical prostatectomy.
A total of 71 patients with clinical stages A1 to B2 adenocarcinoma of the prostate underwent radical prostatectomy after a negative metastatic evaluation. No neoadjuvant or adjuvant treatments were given and causes of death were recorded. Prostatectomy specimens were analyzed to determine the conventional pathological parameters, and p53, Rb and bcl-2 immunohistochemical staining. Univariate and multivariate analyses were done to determine the independent contributions of p53, Rb and bcl-2 in predicting survival.
On multivariate analysis the independent factors predicting disease specific survival were p53 staining score (p < 0.001) and Rb staining score (p < 0.001). In patients with p53 immunoreactive tumors the 15-year disease specific survival was 38% compared to 87% for those with less immunoreactivity. Analysis of Rb immunoreactivity for 15-year disease specific survival yielded 92 and 66% high and low staining levels, respectively. Best subset analysis revealed that the combination of p53 score and Rb score yielded the best predictive value for disease specific survival.
p53 and Rb immunohistochemical staining scores were independent predictors of disease specific survival and were superior to conventional pathological prognostic factors of the primary tumor. These findings lay the groundwork for the prospective study of these markers in patients treated with radical prostatectomy.
p53和bcl-2基因产物的积累以及视网膜母细胞瘤（Rb）基因产物的缺失与前列腺癌进展相关。我们评估了在接受根治性前列腺切除术的临床局限性前列腺癌患者中，p53、Rb和bcl-2免疫反应性水平是否比原发肿瘤的传统病理参数（如Gleason评分、包膜侵犯、精囊侵犯和标本中肿瘤百分比）更能作为疾病特异性生存的长期预测指标。
共有71例临床分期为A1至B2期前列腺腺癌患者在转移评估为阴性后接受了根治性前列腺切除术。未给予新辅助或辅助治疗，并记录死亡原因。对前列腺切除标本进行分析以确定传统病理参数以及p53、Rb和bcl-2免疫组化染色。进行单因素和多因素分析以确定p53、Rb和bcl-2在预测生存方面的独立作用。
多因素分析显示，预测疾病特异性生存的独立因素为p53染色评分（p < 0.001）和Rb染色评分（p < 0.001）。p53免疫反应性肿瘤患者的15年疾病特异性生存率为38%，而免疫反应性较低者为87%。分析Rb免疫反应性对15年疾病特异性生存的影响，高染色水平和低染色水平分别为92%和66%。最佳子集分析显示，p53评分和Rb评分的组合对疾病特异性生存具有最佳预测价值。
p53和Rb免疫组化染色评分是疾病特异性生存的独立预测指标，优于原发肿瘤的传统病理预后因素。这些发现为在接受根治性前列腺切除术的患者中对这些标志物进行前瞻性研究奠定了基础。
