Scherr D S, Vaughan E D, Wei J, Chung M, Felsen D, Allbright R, Knudsen B S
Department of Urology, James Buchanan Brady Foundation, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
J Urol. 1999 Jul;162(1):12-6; discussion 16-7. doi: 10.1097/00005392-199907000-00003.
Clinicians have long been hampered by the inability to distinguish patients with localized prostate cancer who will and will not respond to radiotherapy. In a significant proportion of patients therapy fails as determined by increasing posttreatment serum prostate specific antigen (PSA). We evaluated the expression of 2 key regulators of apoptosis, bcl-2 and p53, relative to treatment outcomes in patients who received external beam radiotherapy for clinically organ confined carcinoma of the prostate.
Immunohistochemical staining for bcl-2 and p53 on pretreatment needle biopsies was performed in 54 patients who were treated with radiotherapy for localized prostate cancer. Expression was scored using strict criteria. Nadir PSA less than 1 ng./ml. after therapy was considered a successful treatment response.
There was a predominance of stage T1c cancer (74%) with a mean Gleason score of 6.9 and an average pretreatment PSA of 25.3 ng./ml. Overall 54% of the patients did not have a nadir PSA of less than 1 ng./ml. Of the bcl-2 positive cases therapy ultimately failed in 85%. Similarly 88% of the patients with p53 positive biopsies had treatment failure and in all with bcl-2 as well as p53 expression radiotherapy failed. Expression of bcl-2 and p53 was an independent prognostic variable for treatment failure with odds ratios (95% confidence interval) of 7.3 and 10.8, respectively.
Expression of bcl-2 and p53 was associated with treatment failure after external beam radiation therapy. These findings suggest that bcl-2 and p53 expression in pretreatment biopsies may be helpful for predicting response to definitive radiotherapy.
长期以来，临床医生一直因无法区分哪些局限性前列腺癌患者会对放疗产生反应、哪些不会而受到困扰。在相当一部分患者中，根据治疗后血清前列腺特异性抗原（PSA）升高情况判断，治疗失败。我们评估了凋亡的两个关键调节因子bcl-2和p53的表达与接受前列腺癌临床局限期外照射放疗患者治疗结果的相关性。
对54例接受局限性前列腺癌放疗的患者进行治疗前穿刺活检组织的bcl-2和p53免疫组化染色。采用严格标准对表达情况进行评分。治疗后最低点PSA低于1 ng/ml被认为是成功的治疗反应。
主要为T1c期癌症（74%），平均Gleason评分为6.9，治疗前平均PSA为25.3 ng/ml。总体而言，54%的患者最低点PSA未低于1 ng/ml。在bcl-2阳性病例中，85%最终治疗失败。同样，p53活检阳性的患者中有88%治疗失败，且所有bcl-2和p53均表达的患者放疗失败。bcl-2和p53的表达是治疗失败的独立预后变量，优势比（95%置信区间）分别为7.3和10.8。
bcl-2和p53的表达与外照射放疗后的治疗失败相关。这些发现表明，治疗前活检中bcl-2和p53的表达可能有助于预测对根治性放疗的反应。
