MAD2 Expression in Ovarian Carcinoma: Different Expression Patterns and Levels among Various Types of Ovarian Carcinoma and Its Prognostic Significance in High-Grade Serous Carcinoma
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Background: Mitotic arrest deficiency protein 2 (MAD2) is a key component of spindle assembly checkpoint function, which mediates cell apoptosis through microtubule kinetics. Aberrant expression of MAD2 is believed to be associated with the development of chromosome instability. MAD2 also has a signihicant role in cellular drug resistance to taxane chemotherapeutic agents. Methods: Expression of MAD2 and p53 was investigated using immunohistochemistry in 85 cases of ovarian carcinomas. Clinicopathological data including progression-free survival were analyzed. Results: A significant (p=.035) association was observed between the grade of serous carcinoma and the expression level of MAD2. While low-grade serous carcinoma showed a lowlevel expression of MAD2, high-grade serous carcinoma showed a high-level expression of MAD2. We also determined that low-level expression of MAD2 was associated with reduced progression-free survival (PFS) (p=.016) in high-grade serous carcinoma. Conclusions: MAD2 expression in ovarian carcinoma is related to the grade of serous carcinoma and PFS of high-grade serous carcinoma. Expression level of MAD2 detected by immunohistochemistry may serve as an indicator in predicting the response of microtubule-interfering chemotherapeutic agents.
Abstract
Background: Mitotic arrest deficiency protein 2 (MAD2) is a key component of spindle assembly checkpoint function, which mediates cell apoptosis through microtubule kinetics. Aberrant expression of MAD2 is believed to be associated with the development of chromosome instability. MAD2 also has a signihicant role in cellular drug resistance to taxane chemotherapeutic agents. Methods: Expression of MAD2 and p53 was investigated using immunohistochemistry in 85 cases of ovarian carcinomas. Clinicopathological data including progression-free survival were analyzed. Results: A significant (p=.035) association was observed between the grade of serous carcinoma and the expression level of MAD2. While low-grade serous carcinoma showed a lowlevel expression of MAD2, high-grade serous carcinoma showed a high-level expression of MAD2. We also determined that low-level expression of MAD2 was associated with reduced progression-free survival (PFS) (p=.016) in high-grade serous carcinoma. Conclusions: MAD2 expression in ovarian carcinoma is related to the grade of serous carcinoma and PFS of high-grade serous carcinoma. Expression level of MAD2 detected by immunohistochemistry may serve as an indicator in predicting the response of microtubule-interfering chemotherapeutic agents.
참고문헌 (21)
- Kurman RJ, "Blaustein’s pathology of the female genital tract", pp.680~ (2011), Springer
- Yu H, "Structural activation of Mad2 in the mitotic spindle checkpoint: the two-state Mad2 model versus the Mad2 template model", J Cell Biol, 173, pp.153~157 (2006)
- Wang L, "MAD2 as a key component of mitotic checkpoint: a probable prognostic factor for gastric cancer", Am J Clin Pathol, 131, pp.793~801 (2009)
- Chen X, "Gene expression patterns in human liver cancers", Mol Biol Cell, 13, pp.1929~1939 (2002)
- Hisaoka M, "Aberrant MAD2 expression in soft-tissue sarcoma", Pathol Int, 58, pp.329~333 (2008)
- Kato T, "Overexpression of MAD2 predicts clinical outcome in primary lung cancer patients", Lung Cancer, 74, pp.124~131 (2011)
- Rimkus C, "Expression of the mitotic checkpoint gene MAD2L2 has prognostic significance in colon cancer", Int J Cancer, 120, pp.207~211 (2007)
- Tanaka K, "Mitotic checkpoint protein hsMAD2 as a marker predicting liver metastasis of human gastric cancers", Jpn J Cancer Res, 92, pp.952~958 (2001)
- Yu L, "Upregulation of Mad2 facilitates in vivo and in vitro osteosarcoma progression", Oncol Rep, 28, pp.2170~2176 (2012)
- Sotillo R, "Mad2 overexpression promotes aneuploidy and tumorigenesis in mice", Cancer Cell, 11, pp.9~23 (2007)
- Schvartzman JM, "Mad2 is a critical mediator of the chromosome instability observed upon Rb and p53 pathway inhibition", Cancer Cell, 19, pp.701~714 (2011)
- Kurman RJ, "Blaustein’s pathology of the female genital tract", pp.729~730 (2011), Springer
- Kurman RJ, "Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications", Int J Gynecol Pathol, 27, pp.151~160 (2008)
- Arik D, "p53, bcl-2, and nm23 expressions in serous ovarian tumors: correlation with the clinical and histopathological parameters", Turk Patoloji Derg, 27, pp.38~45 (2011)
- Malamou-Mitsi V, "Prognostic significance of HER-2, p53 and Bcl-2 in patients with epithelial ovarian cancer", Anticancer Res, 27, pp.1157~1165 (2007)
- Morishita M, "Expression of mitotic-arrest deficiency 2 predicts the efficacy of neoadjuvant chemotherapy for locally advanced uterine cervical cancer", Exp Ther Med, 3, pp.341~346 (2012)
- Nakano Y, "Expression of the mitotic-arrest deficiency 2 is associated with chemotherapy resistance in ovarian serous adenocarcinoma", Oncol Rep, 28, pp.1200~1204 (2012)
- Furlong F, "Low MAD2 expression levels associate with reduced progression-free survival in patients with high-grade serous epithelial ovarian cancer", J Pathol, 226, pp.746~755 (2012)
- Fung MK, "MAD2 expression and its significance in mitotic checkpoint control in testicular germ cell tumour", Biochim Biophys Acta, 1773, pp.821~832 (2007)
- Fung MK, "Role of MEK", ERK pathway in the MAD2-mediated cisplatin sensitivity in testicular germ cell tumour cells, 2006, pp.95, 475~484
- Wang X, "Significance of MAD2 expression to mitotic checkpoint control in ovarian cancer cells", Cancer Res, 62, pp.1662~1668 (2002)