title: Expression of aurora kinases: Predictor of tumor dissemination in uterine carcinosarcoma.
abstract: Uterine carcinosarcoma is a rare, aggressive, and biphasic tumor. It comprises carcinomatous and sarcomatous components, and mitosis-associated factors are thought to discriminate these two lesions. Aurora kinases are mitotic enzymes that are highly expressed in uterine malignancies. To identify the clinical significance of aurora kinase expression, we performed immunohistochemistry on tissue microarrays using cores selected from areas with typical carcinomatous and sarcomatous characteristics. A total of 24 samples were included, from patients at Seoul National University Hospital diagnosed with uterine carcinosarcoma, and who undergone a staging operation between 1997 and 2012. Patients' clinical and pathological data were analyzed, and expression patterns of aurora kinases were investigated. Aurora kinases A and B were dominantly expressed in the cytoplasm, and phospho-aurora kinases A and B were expressed in the nuclei. Phospho-aurora kinase A and aurora kinase B showed significantly higher expression in the carcinomatous component (P=0.012 and 0.008). High expression of phospho-aurora kinase A was associated with lymphatic metastasis such as positive pelvic lymph node and omental involvement (P=0.012 and 0.037). Overexpression of aurora kinase B was related to vascular invasion (P=0.011). High expression of both phospho-aurora kinase A and aurora kinase B was a prognostic factor for progression-free survival in uterine carcinosarcoma (P=0.049). In conclusion, expression of aurora kinases is associated with bidirectional tumor dissemination into the lymphatic and hematogenous pathways. In addition, high expression of phospho-aurora kinase A and aurora kinase B is a predictor of progression-free survival. Therefore, inhibitors of aurora kinases might be a prospective therapeutic options for uterine carcinosarcoma.
authors: Department of Obstetrics and Gynecology, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea.
authors: Kyung Hee
authors: KH
authors: Han
authors: Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Min A
authors: MA
authors: Kim
authors: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea. pnhkhr@snu.ac.kr.
authors: Noh Hyun
authors: NH
authors: Park
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D064096:Aurora Kinase A / Q000378:metabolism; D064107:Aurora Kinase B / Q000378:metabolism; D064127:Aurora Kinases / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor; D002296:Carcinosarcoma / Q000201:enzymology* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008593:Menopause; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D014594:Uterine Neoplasms / Q000201:enzymology* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C576917:AURKA protein, human; C576921:AURKB protein, human; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases