Lassmann Silke, Shen Yi, Jütting Uta, Wiehle Philipp, Walch Axel, Gitsch Gerald, Hasenburg Annette, Werner Martin
Institute of Pathology, University Hospital, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
Clin Cancer Res. 2007 Jul 15;13(14):4083-91. doi: 10.1158/1078-0432.CCR-06-2775.
To investigate the expression and regulation of the centrosomal kinase Aurora-A/STK15 (AURKA) in epithelial ovarian cancers and to determine the prognostic and predictive value of this marker for patients with late stage epithelial ovarian cancer treated by distinct adjuvant chemotherapies.
Archival resection specimens of epithelial ovarian cancers (n=115) and nonneoplastic ovaries (n=28) were analyzed for AURKA mRNA and protein expression by microdissection and quantitative reverse transcriptase-PCR and immunohistochemistry. AURKA DNA copy numbers were measured by fluorescence in situ hybridization in 37 cases. Statistical evaluation was done with respect to clinicopathologic variables, disease-free survival, and overall survival.
AURKA mRNA expression was significantly elevated in cancers (P<0.001) and correlated with AURKA protein expression (P=0.0134). Overexpression of AURKA protein was detected in 68 of 107 (63.5%) cases and was linked with increased AURKA DNA copy numbers (P=0.0141) and centromere 20 aneusomy (P=0.0137). Moreover, AURKA overexpression was associated with improved overall survival in optimal debulked patients receiving taxol/carboplatin therapy (n=43, P=0.018). Finally, in an exploratory approach, patients receiving non-taxane-based therapy, AURKA overexpression was predictive for worse overall survival (n=30, P=0.049).
AURKA overexpression is seen in the majority of late stage epithelial ovarian cancers, most likely due to increased AURKA DNA copy numbers and/or chromosome 20 aneusomy. Importantly, AURKA overexpression may differentially affect taxane and non-taxane-based adjuvant therapy responses. The study sheds new light on AURKA expression and regulation in epithelial cancers in vivo and specifically shows its value as a clinically relevant marker and as a potential therapeutic target per se.
研究中心体激酶极光激酶A/ASTK15（AURKA）在上皮性卵巢癌中的表达及调控情况，并确定该标志物对接受不同辅助化疗的晚期上皮性卵巢癌患者的预后及预测价值。
采用显微切割及定量逆转录聚合酶链反应和免疫组织化学方法，分析115例上皮性卵巢癌存档切除标本及28例非肿瘤性卵巢标本中AURKA mRNA和蛋白的表达情况。采用荧光原位杂交技术检测37例患者的AURKA DNA拷贝数。针对临床病理变量、无病生存期和总生存期进行统计学评估。
癌组织中AURKA mRNA表达显著升高（P<0.001），且与AURKA蛋白表达相关（P=0.0134）。107例患者中有68例（63.5%）检测到AURKA蛋白过表达，且与AURKA DNA拷贝数增加（P=0.0141）及20号染色体着丝粒非整倍体相关（P=0.0137）。此外，在接受紫杉醇/卡铂治疗且肿瘤细胞减灭术达到理想效果的患者中（n=43，P=0.018），AURKA过表达与总生存期改善相关。最后，在一项探索性研究中，接受非紫杉烷类治疗的患者中，AURKA过表达提示总生存期较差（n=30，P=0.049）。
大多数晚期上皮性卵巢癌中可见AURKA过表达，很可能是由于AURKA DNA拷贝数增加和/或20号染色体非整倍体所致。重要的是，AURKA过表达可能对基于紫杉烷类和非紫杉烷类的辅助治疗反应产生不同影响。该研究为体内上皮性癌中AURKA的表达及调控提供了新的线索，并特别显示出其作为临床相关标志物及潜在治疗靶点本身的价值。
