Predictive value of Aurora-A/STK15 expression for late stage epithelial ovarian cancer patients treated by adjuvant chemotherapy.
ABSTRACT 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.
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ABSTRACT: Purpose To investigate the expression of Aurora Kinase A and B in patients with chondrosarcoma and consider it as a prognostic marker and molecular target of therapy. METHODS: To evaluate the relationship of the Aurora Kinase A and B and the clinical pathological parameters and prognosis of chondrosarcoma. 72 case chondrosarcoma and 42 case chondroma were performed immunohistochemistry on the tissue microarray paraffin sections. The survival time of patients was followed-up. RESULTS: The expression of Aurora Kinase A and B in chondrosarcoma was significantly higher than that in chondroma (p<0.01). There were differences about the expression of Aurora Kinase A and B in chondrosarcoma between the recurrence group and the non-recurrence group, metastatic group and non-metastatic group (p<0.05), but not age and gender (p>0.05). The expression of Aurora Kinase A and B were significantly lower in group low grade conventional chondrosarcoma than that in groups medium and high grade conventional chondrosarcoma (p<0.01). The expression of Aurora Kinase A and B in chondrosarcoma showed a positive correlation (p<0.01). According to the Kaplan Meier analysis and multivariate Cox regression analysis, the survival rate was significantly different between the patients with positive Aurora Kinase A and the patients with negative expression (p<0.05) and Aurora Kinase A expression was an independent risk marker of survival(HR=11.263, 95%CI: 2.317-54.748, P=0.003). CONCLUSION: Both the Aurora Kinase A and B might involve in the oncogenic, invasive and metastatic process of chondrosarcoma; however, the mechanism is still unclear. The Aurora Kinase A and B could be used as a new prognostic marker and molecular therapeutic target for chondrosarcoma. Virtual Slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9101494267377096.Diagnostic Pathology 07/2012; 7(1):84. · 1.85 Impact Factor
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ABSTRACT: For completely resected primary gastrointestinal stromal tumors (GISTs), mitotic rate, tumor size, and tumor location are important risk factors for recurrence. However, molecular markers for recurrence are still lacking. We reanalyzed GIST gene expression profile GSE8167 available from the Gene Expression Omnibus (GEO) and confirmed the prognostic influence of one selected gene, aurora kinase A (AURKA), in another cohort of 142 patients using immunohistochemistry (IHC). Thirty-two cases in GSE8167 were classified into two risk groups with distinct recurrence-free survival (RFS) and expression profiles using modified criteria of Miettinen et al. from the Armed Forces Institute of Pathology (AFIP-Miettinen). AURKA was among the 19 genes common to the top 50 features of the high-risk phenotype and a 67-gene signature called the complexity index in sarcomas. AURKA was significantly overexpressed in the high-risk group, and patients with high AURKA expression had significantly worse RFS than those with low expression. In the IHC-validated cohort, AURKA expression was significantly higher in nongastric tumors than in gastric tumors and was significantly correlated with AFIP-Miettinen risk group. Univariate analysis showed that RFS was significantly influenced by tumor size, mitotic count, AFIP-Miettinen risk group classification, and AURKA expression. However, only tumor size (P = 0.017), mitotic count (P = 0.007), and AURKA expression (P = 0.039) were identified as independent unfavorable prognostic factors for RFS in multivariate analysis. By integrating bioinformatics and clinicopathological studies, AURKA was identified as a marker for high-risk GIST.Annals of Surgical Oncology 05/2012; 19(11):3491-9. · 4.12 Impact Factor
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ABSTRACT: Solitary fibrous tumors (SFTs) are rare spindle-cell tumors. Their cell-of-origin and molecular basis are poorly known. They raise several clinical problems. Differential diagnosis may be difficult, prognosis is poorly apprehended by histoclinical features, and no effective therapy exists for advanced stages. We profiled 16 SFT samples using whole-genome DNA microarrays and analyzed their expression profiles with publicly available profiles of 36 additional SFTs and 212 soft tissue sarcomas (STSs). Immunohistochemistry was applied to validate the expression of some discriminating genes. SFTs displayed whole-genome expression profiles more homogeneous and different from STSs, but closer to genetically-simple than genetically-complex STSs. The SFTs/STSs comparison identified a high percentage (∼30%) of genes as differentially expressed, most of them without any DNA copy number alteration. One of the genes most overexpressed in SFTs encoded the ALDH1 stem cell marker. Several upregulated genes and associated ontologies were also related to progenitor/stem cells. SFTs also overexpressed genes encoding therapeutic targets such as kinases (EGFR, ERBB2, FGFR1, JAK2), histone deacetylases, or retinoic acid receptors. Their overexpression was found in all SFTs, regardless the anatomical location. Finally, we identified a 31-gene signature associated with the mitotic count, containing many genes related to cell cycle/mitosis, including AURKA. We established a robust repertoire of genes differentially expressed in SFTs. Certain overexpressed genes could provide new diagnostic (ALDH1A1), prognostic (AURKA) and/or therapeutic targets.PLoS ONE 01/2013; 8(5):e64497. · 3.73 Impact Factor