Department of Pathology and Laboratory Medicine, University of Calgary-Cumming School of Medicine, Calgary, AB, Canada.
Departments of Oncology, Biochemistry and Molecular Biology, University of Calgary-Cumming School of Medicine, Calgary, AB, Canada.
J Cancer Res Clin Oncol. 2018 Nov;144(11):2117-2125. doi: 10.1007/s00432-018-2730-5. Epub 2018 Aug 12.
To assess the prognostic value of ERG and PTEN protein expression as two of the most common genetic aberration in men with prostate cancer managed non-surgically by androgen deprivation therapy (ADT).
463 tumor samples were assessed by double immunohistochemistry stains for ERG and PTEN and data correlated with clinical pathological features including, Gleason score, patients' outcome and ADT.
ERG expression and PTEN protein loss were present in 28.2% and 38% of total patients respectively. There was a significant interplay between ERG and PTEN expression with 21.8% PTEN negative tumors being ERG positive (p < 0.001). Both ERG and PTEN showed significant association with lethal disease in all patients and those treated with prior ADT representing castrate-resistant disease. However, only PTEN remained significant in multivariable proportional hazards regression analysis, when including Gleason score and patients' age. Depending on patient's subgroup, intact positive PTEN intensity showed better cancer-specific survival with HR ranging from 0.25 to 0.4 compared to tumors with loss of PTEN expression. Assessing combined marker status, patients with decreased PTEN intensity without ERG positivity showed the worst clinical outcome compared to those with no PTEN loss and no ERG expression, where they had best clinical outcome. Patients with ERG expression with or without PTEN loss showed intermediate risk in relation to lethal disease.
This study confirms a significant prognostic role for assessing ERG and PTEN in men with prostate cancer. It supports a role for utilizing combined ERG/PTEN status clinically and prospectively for stratifying PCa patients into different prognostic groups.
评估 ERG 和 PTEN 蛋白表达作为两种最常见的遗传异常在接受雄激素剥夺治疗（ADT）的非手术治疗的前列腺癌男性中的预后价值。
对 463 例肿瘤样本进行 ERG 和 PTEN 的双重免疫组织化学染色，并将数据与临床病理特征相关联，包括 Gleason 评分、患者预后和 ADT。
ERG 表达和 PTEN 蛋白缺失分别存在于 28.2%和 38%的患者中。ERG 表达和 PTEN 缺失之间存在显著的相互作用，21.8%的 PTEN 阴性肿瘤呈 ERG 阳性（p<0.001）。在所有患者以及接受过 ADT 治疗的患者中，ERG 和 PTEN 均与致命性疾病显著相关，这些患者代表去势抵抗性疾病。然而，仅在包括 Gleason 评分和患者年龄在内的多变量比例风险回归分析中，PTEN 仍然具有显著意义。根据患者亚组的不同，完整的阳性 PTEN 强度显示出更好的癌症特异性生存，HR 范围从 0.25 到 0.4，与 PTEN 表达缺失的肿瘤相比。评估联合标志物状态，与没有 PTEN 丢失和没有 ERG 表达的患者相比，PTEN 强度降低而没有 ERG 阳性的患者显示出最差的临床结局，他们具有最佳的临床结局。ERG 表达而没有 PTEN 缺失的患者与致命性疾病相关的风险处于中间水平。
本研究证实了评估 ERG 和 PTEN 在前列腺癌男性中的预后具有重要作用。它支持在临床上和前瞻性地利用 ERG/PTEN 状态将前列腺癌患者分层为不同的预后组。
