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Expression of aurora kinases (aurora kinase A, aurora kinase B, phospho-aurora kinase A, and phospho-aurora kinase B) in uterine carcinosarcoma
자궁 암육종에서 aurora kinases 발현에 관한 연구

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Authors
한경희
Advisor
박노현
Major
의과대학 의학과
Issue Date
2013-02
Publisher
서울대학교 대학원
Keywords
uterine carcinosarcomaaurora kinaseimmunohistochemistry
Description
학위논문 (석사)-- 서울대학교 대학원 : 의학과 산부인과 전공, 2013. 2. 박노현.
Abstract
Introduction: Uterine carcinosarcoma (UCS) is an uncommon, biphasic uterine cancer which comprised of both a sarcomatous component (SC) and a carcinomatous component (CC). Despite some controversies on prognosis, CC is accepted as having potential for tumor progression and metastasis. As a driving force, CC induces sarcomatous metaplasia to form SC. Because CC has usually high mitotic count, expression patterns of mitotic kinase would be different between SC and CC. Aurora kinases are involved in separation and arrangement of chromosome, attachment of microtubule, and cytokinesis during mitosis. They regulate the G2/M phase, and contribute to carcinogenesis via abnormal cell proliferation and ceased apoptosis. The aim of this study is to investigate the expression pattern of aurora kinases according to the histologic components of UCS.

Methods: Typical areas for SC and CC were used to make tissue microarray cores. Immunohistochemistry was performed with antibodies for aurora kinase A (AURKA), aurora kinase B (AURKB), phospho-aurora kinase A (p-AURKA), and phospho-aurora kinase B (p-AURKB). The expression score was assessed by multiplying the intensity and cell proportion in nucleus and cytoplasm. For AURKA and AURKB, high expression was defined as ≥ 30% positive tumor cells in the selected area. In p-AURKA and p-AURKB, samples with total score ≥ 6 were regarded as high expression. Medical records were retrospectively reviewed for clinical correlation.

Results: Histologic subtypes of SC were evenly divided into homologous and heterologous type. Most of the histology of CC was endometrioid (8/24, 33.3%), and others were serous (5/24, 20.8%), mucinous (1/24, 4.2%), adenosquamous type (5/24, 20.8%). Nuclear expression score of AURKB was much higher in CC than in SC (p=0.041). Polo-like kinase 1 expression was interrelated -with aurora kinases expression in cytoplasm and correlated with phosphorylated aurora kinases expression in nucleus. Nuclear expression of p-AURKA in CC was involved in tumor stage, lymph node metastasis, and omental involvement (p=0.027, 0.012, 0.037, respectively). Cytoplasmic expression of AURKB in CC and nuclear expression of p-AURKB in SC were correlated with positive vascular invasion (p=0.011 and 0.006).

Conclusions: The expression patterns of aurora kinases in UCS are involved in disease progression and vascular invasion. In addition, CC was the main part to express aurora kinases. This result supports the sarcomatous metaplasia, similar to the process of epithelial to mesenchymal transition. Inhibitors of aurora kinases are perspective chemotherapeutics for UCS.
Language
English
URI
https://hdl.handle.net/10371/132571
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Theses (Master's Degree_의학과)
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