Augustin H, Freibauer C, Bayer L, Lunglmayr G, Tschurlovich F, Kuber W, Pummer K
Department of Urology, LKH Graz, Medical University of Graz, Graz, Austria.
Prostate Cancer Prostatic Dis. 2006;9(3):279-83. doi: 10.1038/sj.pcan.4500883. Epub 2006 May 16.
Tumour features were evaluated during intermittent androgen suppression (IAS), and their prognostic impact on the first off-treatment time was analysed.
Twenty patients with advanced prostate cancer underwent three consecutive prostate biopsies during the first cycle, namely at the beginning of androgen deprivation, 8 months after continuous therapy and at the time of prostate-specific antigen (PSA) progression above 20 ng/ml. Biopsy specimens were immunohistochemically processed and analysed for the apoptotic index (AI), Ki-67, p53 and Bcl-2 to investigate eventual changes over time. Correlations and regression analysis were performed to assess the prognostic significance of clinical and pathological parameters in predicting the first off-treatment time.
In contrast to the AI, p53 and Bcl-2, Ki-67 was the only marker that significantly changed over time (P=0.008). The first off-treatment time correlated significantly with pretreatment PSA (r=-0.594; P<0.01), testosterone recovery time (r=0.590; P=0.013) and biopsy grade (r=-0.738; P<0.01); only the latter gaining an independent factor in the multivariate analysis (P=0.022).
During IAS, Ki-67 was the only molecular marker that consistently changed over time. However, it did not correlate with off-treatment time that was predicted independently by the initial biopsy grade only. First off-treatment time was best predicted by clinical parameters and molecular markers from needle biopsies did not further contribute to a better patient selection.
在间歇性雄激素抑制（IAS）期间评估肿瘤特征，并分析其对首次停止治疗时间的预后影响。
20例晚期前列腺癌患者在第一个周期内连续接受三次前列腺活检，分别在雄激素剥夺开始时、持续治疗8个月后以及前列腺特异性抗原（PSA）进展至高于20 ng/ml时。对活检标本进行免疫组织化学处理，并分析凋亡指数（AI）、Ki-67、p53和Bcl-2，以研究随时间的最终变化。进行相关性和回归分析，以评估临床和病理参数在预测首次停止治疗时间方面的预后意义。
与AI、p53和Bcl-2不同，Ki-67是唯一随时间有显著变化的标志物（P = 0.008）。首次停止治疗时间与治疗前PSA显著相关（r = -0.594；P < 0.01）、睾酮恢复时间（r = 0.590；P = 0.013）和活检分级（r = -0.738；P < 0.01）；在多变量分析中只有后者成为独立因素（P = 0.022）。
在IAS期间，Ki-67是唯一随时间持续变化的分子标志物。然而，它与仅由初始活检分级独立预测的停止治疗时间无关。首次停止治疗时间最好由临床参数预测，针吸活检的分子标志物并未进一步有助于更好地选择患者。
