Predictive value of Aurora-A/STK15 expression for late stage epithelial ovarian cancer patients treated by adjuvant chemotherapy.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Lassmann
Silke
S
Institute of Pathology, University Hospital, Albert-Ludwigs-University Freiburg, Freiburg, Germany. silke.lassmann@uniklinik-freiburg.de
Shen
Yi
Y
Jütting
Uta
U
Wiehle
Philipp
P
Walch
Axel
A
Gitsch
Gerald
G
Hasenburg
Annette
A
Werner
Martin
M
D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D011237:Predictive Value of Tests; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016019:Survival Analysis
D000970:Antineoplastic Agents; D012333:RNA, Messenger; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases