Ferraldeschi Roberta, Nava Rodrigues Daniel, Riisnaes Ruth, Miranda Susana, Figueiredo Ines, Rescigno Pasquale, Ravi Praful, Pezaro Carmel, Omlin Aurelius, Lorente David, Zafeiriou Zafeiris, Mateo Joaquin, Altavilla Amelia, Sideris Spyridon, Bianchini Diletta, Grist Emily, Thway Khin, Perez Lopez Raquel, Tunariu Nina, Parker Chris, Dearnaley David, Reid Alison, Attard Gerhardt, de Bono Johann
Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
Academic Urology Unit, The Royal Marsden NHS Foundation Trust, London, UK.
Eur Urol. 2015 Apr;67(4):795-802. doi: 10.1016/j.eururo.2014.10.027. Epub 2014 Nov 4.
Loss of the tumor suppressor phosphatase and tensin homolog (PTEN) occurs frequently in prostate cancers. Preclinical evidence suggests that activation of PI3K/AKT signaling through loss of PTEN can result in resistance to hormonal treatment in prostate cancer.
To explore the antitumor activity of abiraterone acetate (abiraterone) in castration-resistant prostate cancer (CRPC) patients with and without loss of PTEN protein expression.
DESIGN, SETTING, AND PARTICIPANTS: We retrospectively identified patients who had received abiraterone and had hormone-sensitive prostate cancer (HSPC) and/or CRPC tissue available for PTEN immunohistochemical analysis.
The primary end point was overall survival from initiation of abiraterone treatment. Relationship with outcome was analyzed using multivariate Cox regression and log-rank analyses.
A total of 144 patients were identified who had received abiraterone post-docetaxel and had available tumor tissue. Overall, loss of PTEN expression was observed in 40% of patients. Matched HSPC and CRPC tumor biopsies were available for 41 patients. PTEN status in CRPC correlated with HSPC in 86% of cases. Loss of PTEN expression was associated with shorter median overall survival (14 vs 21 mo; hazard ratio [HR]: 1.75; 95% confidence interval [CI], 1.19-2.55; p=0.004) and shorter median duration of abiraterone treatment (24 vs 28 wk; HR: 1.6; 95% CI, 1.12-2.28; p=0.009). PTEN protein loss, high lactate dehydrogenase, and the presence of visceral metastases were identified as independent prognostic factors in multivariate analysis.
Our results indicate that loss of PTEN expression was associated with worse survival and shorter time on abiraterone treatment. Further studies in larger and prospective cohorts are warranted.
PTEN is a protein often lost in prostate cancer cells. In this study we evaluated if prostate cancers that lack this protein respond differently to treatment with abiraterone acetate. We demonstrated that the survival of patients with loss of PTEN is shorter than patients with normal PTEN expression.
肿瘤抑制因子磷酸酶和张力蛋白同源物（PTEN）的缺失在前列腺癌中频繁发生。临床前证据表明，通过PTEN缺失激活PI3K/AKT信号传导可导致前列腺癌对激素治疗产生耐药性。
探讨醋酸阿比特龙（阿比特龙）在PTEN蛋白表达缺失和未缺失的去势抵抗性前列腺癌（CRPC）患者中的抗肿瘤活性。
设计、设置和参与者：我们回顾性地确定了接受过阿比特龙治疗且有激素敏感性前列腺癌（HSPC）和/或CRPC组织可用于PTEN免疫组织化学分析的患者。
主要终点是从开始阿比特龙治疗起的总生存期。使用多变量Cox回归和对数秩分析来分析与结果的关系。
共确定了144例接受过阿比特龙治疗且有可用肿瘤组织的患者。总体而言，40%的患者观察到PTEN表达缺失。41例患者有匹配的HSPC和CRPC肿瘤活检样本可用。在86%的病例中，CRPC中的PTEN状态与HSPC相关。PTEN表达缺失与较短的中位总生存期（14个月对21个月；风险比[HR]：1.75；95%置信区间[CI]，1.19 - 2.55；p = 0.004）和较短的阿比特龙治疗中位持续时间（24周对28周；HR：1.6；95% CI，1.12 - 2.28；p = 0.009）相关。在多变量分析中，PTEN蛋白缺失、高乳酸脱氢酶和内脏转移的存在被确定为独立的预后因素。
我们的结果表明，PTEN表达缺失与较差的生存率和较短的阿比特龙治疗时间相关。有必要在更大的前瞻性队列中进行进一步研究。
PTEN是一种在前列腺癌细胞中经常缺失的蛋白质。在本研究中，我们评估了缺乏这种蛋白质的前列腺癌对醋酸阿比特龙治疗的反应是否不同。我们证明，PTEN缺失患者的生存期短于PTEN表达正常的患者。
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