Wissing Michel D, De Morrée Ellen S, Dezentjé Vincent O, Buijs Jeroen T, De Krijger Ronald R, Smit Vincent T H B M, Van Weerden Wytske M, Gelderblom Hans, van der Pluijm Gabri
Department of Clinical Oncology, Leiden University Medical Center, Leiden, the Netherlands. Department of Urology, Leiden University Medical Center, Leiden, the Netherlands. Contributed equally to this work.
Department of Urology, Erasmus MC-Cancer Institute, Rotterdam, the Netherlands. Contributed equally to this work.
Oncotarget. 2014 Sep 15;5(17):7357-67. doi: 10.18632/oncotarget.1985.
Novel biomarkers predicting prostate cancer (PCa) aggressiveness and docetaxel therapy response of PCa patients are needed. In this study the correlation between nuclear Eg5-expression, PCa docetaxel response and PCa aggressiveness was assessed. Immunohistochemical staining for nuclear Eg5 was performed on 117 archival specimens from 110 PCa patients treated with docetaxel between 2004 and 2012. Samples were histologically categorized as positive/negative. Median follow-up time from diagnosis was 11.6 years. Nuclear Eg5-expression was significantly related to docetaxel response (p=0.036) in tissues acquired within three years before docetaxel initiation. Nuclear Eg5-expression was not related to Gleason-score (p=0.994). Survival of patients after docetaxel initiation did not differ based on nuclear Eg5-expression (p=0.540). Analyzing samples taken before hormonal therapy, overall survival and time to docetaxel use were significantly decreased in patients with nuclear Eg5-expressing tumors (p<0.01). Eg5-positive nuclei were found more frequently in T4-staged tumors (p=0.04), Gleason 8-10 tumors (p=0.08), and in metastasized tumors (p<0.01). Multivariate analyses indicated that nuclear Eg5-expression may be an independent parameter for tumor aggressiveness. Limitations of a retrospective analysis apply. In conclusion, nuclear Eg5-expression may be a predictive biomarker for docetaxel response in metastatic castrate-resistant PCa patients and a prognostic biomarker for hormone-naive PCa patients. Prospective validation studies are needed.
需要能够预测前列腺癌（PCa）侵袭性以及PCa患者多西他赛治疗反应的新型生物标志物。在本研究中，评估了核Eg5表达、PCa多西他赛反应与PCa侵袭性之间的相关性。对2004年至2012年间接受多西他赛治疗的110例PCa患者的117份存档标本进行了核Eg5免疫组织化学染色。样本在组织学上分为阳性/阴性。从诊断开始的中位随访时间为11.6年。在开始多西他赛治疗前三年之内获取的组织中，核Eg5表达与多西他赛反应显著相关（p=0.036）。核Eg5表达与 Gleason评分无关（p=0.994）。开始多西他赛后患者的生存率根据核Eg5表达没有差异（p=0.540）。分析激素治疗前采集的样本，核Eg5表达阳性肿瘤患者的总生存期和开始使用多西他赛的时间显著缩短（p<0.01）。在T4期肿瘤（p=0.04）、Gleason 8-10级肿瘤（p=0.08）和转移瘤（p<0.01）中，Eg5阳性核更常见。多变量分析表明，核Eg5表达可能是肿瘤侵袭性的一个独立参数。本研究存在回顾性分析的局限性。总之，核Eg5表达可能是转移性去势抵抗性PCa患者多西他赛反应的预测生物标志物，也是激素初治PCa患者的预后生物标志物。需要进行前瞻性验证研究。
