An immunohistochemical signature comprising PTEN, MYC, and Ki67 predicts progression in prostate cancer patients receiving adjuvant docetaxel after prostatectomy.
An immunohistochemical signature comprising PTEN, MYC, and Ki67 predicts progression in prostate cancer patients receiving adjuvant docetaxel after prostatectomy.
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DOI：
10.1002/cncr.27689
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发表时间：
2012-12-15
期刊：
影响因子：
6.2
通讯作者：
Eisenberger, Mario A.
中科院分区：
文献类型：
--
作者：
Antonarakis, Emmanuel S.;Keizman, Daniel;Zhang, Zhe;Gurel, Bora;Lotan, Tamara L.;Hicks, Jessica L.;Fedor, Helen L.;Carducci, Michael A.;De Marzo, Angelo M.;Eisenberger, Mario A.
关键词：
抑癌基因PTEN的缺失在前列腺癌中很常见，可能对预后有意义。作者在一项前瞻性多中心试验(TAX2501)中检测了接受多西他赛辅助治疗的高危局限性前列腺癌患者的原发肿瘤中的PTEN和其他蛋白标记物。在参加TAX2501的77例患者中，56例接受了初次前列腺切除标本，用于PTEN、MYC、ERG、肿瘤蛋白P53(P53)、抗原Ki-67(Ki67)、Akt的磷酸化形式、哺乳动物雷帕霉素靶标(MTOR)和S6核糖体蛋白的免疫组织化学分析。方案定义的进展包括前列腺特异性抗原(PSA)水平≥0.4 ng/mL，放射学/临床复发，或死亡。采用单因素和多变量比例风险回归分析研究PTEN状态(和其他蛋白标记物)对无进展生存率(PFS)的影响。在这项探索性的术后分析中，61%的患者观察到PTEN蛋白缺失(VS)，并与术前较低的PSA水平、较高的临床分期、较低的Ki67表达、P53的存在和ERG的存在有关。在单因素分析中，与PFS相关的因素包括Gleason sum、精囊侵犯、PTEN状态、MYC表达和Ki67表达。在多变量分析中，只有3个变量作为PFS的独立预后因素：PTEN状态(P=.035)、MYC表达(P=.001)和Ki67表达(P=.001)。我们构建了一个包含临床协变量以及PTEN、MYC和Ki67信息的预后模型。目前的结果表明，在前列腺癌高危患者接受前列腺癌切除术后辅助性多西紫杉醇治疗的患者中，原发肿瘤样本中PTEN状态、MYC表达和Ki67表达可能比单独使用临床因素更准确地预测PFS。如果得到证实，这些假设生成的发现可能具有预后和治疗意义，并可能有助于临床试验设计。
Loss of the tumor suppressor PTEN is common in prostate cancer and may have prognostic significance. The authors examined PTEN and additional protein markers in primary tumors from patients with high-risk, localized prostate cancer who received adjuvant docetaxel in a prospective multicenter trial (TAX2501). Fifty-six of 77 patients enrolled in TAX2501 had primary prostatectomy specimens available for immunohistochemical analysis of PTEN, MYC, ERG, tumor protein p53 (p53), antigen KI-67 (Ki67), and phosphorylated forms of Akt, mammalian target of rapamycin (mTOR), and S6 ribosomal protein. Protocol-defined progression included a prostate-specific antigen (PSA) level ≥0.4 ng/mL, radiologic/clinical recurrence, or death. Univariate and multivariable proportional hazards regression analyses were used to investigate the influence of PTEN status (and other protein markers) on progression-free survival (PFS). In this exploratory, post hoc analysis, PTEN protein loss (vs presence) was observed in 61% of patients and was associated with lower preoperative PSA levels, higher clinical stage, lower Ki67 expression, the presence of p53, and the presence of ERG. In univariate analysis, the factors associated with PFS included Gleason sum, seminal vesicle invasion, PTEN status, MYC expression, and Ki67 expression. In multivariable analysis, only 3 variables emerged as independent prognostic factors for PFS: PTEN status (P = .035), MYC expression (P = .001), and Ki67 expression (P < .001). A prognostic model was constructed that incorporated clinical covariates as well as information on PTEN, MYC, and Ki67. The current results indicated that PTEN status, MYC expression, and Ki67 expression in primary tumor samples may predict PFS more accurately than clinical factors alone in men with high-risk prostate cancer who receive adjuvant docetaxel after prostatectomy. If validated, these hypothesis-generating findings may have prognostic and therapeutic implications and may aid clinical trial design.
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影响因子：
6.6
作者：
Han, M;Partin, AW;Walsh, PC
通讯作者：
Walsh, PC
影响因子：
5.6
作者：
Chaux, Alcides;Albadine, Roula;Netto, George J.
通讯作者：
Netto, George J.
前列腺癌中的ERG癌蛋白表达：ERG阳性肿瘤细胞的克隆进展和基于ERG的分层的潜力。
影响因子：
4.8
作者：
Furusato, B.;Tan, S-H;Young, D.;Dobi, A.;Sun, C.;Mohamed, A. A.;Thangapazham, R.;Chen, Y.;McMaster, G.;Sreenath, T.;Petrovics, G.;McLeod, D. G.;Srivastava, S.;Sesterhenn, I. A.
通讯作者：
Sesterhenn, I. A.
影响因子：
50.3
作者：
Mulholland DJ;Tran LM;Li Y;Cai H;Morim A;Wang S;Plaisier S;Garraway IP;Huang J;Graeber TG;Wu H
通讯作者：
Wu H
DOI：
10.1186/bcr2719
发表时间：
2010
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Pinhel IF;Macneill FA;Hills MJ;Salter J;Detre S;A'hern R;Nerurkar A;Osin P;Smith IE;Dowsett M
通讯作者：
Dowsett M