Skip to main content
Top
Published in: Journal of Ovarian Research 1/2016

Open Access 01-12-2016 | Research

EphA5 protein, a potential marker for distinguishing histological grade and prognosis in ovarian serous carcinoma

Authors: Xiao Chen, Xuan Wang, Xue Wei, Jiandong Wang

Published in: Journal of Ovarian Research | Issue 1/2016

Login to get access

Abstract

Background

Ovarian serous carcinoma (OSC) is the most common ovarian epithelial malignancy. Disregulation of Eph/ephrin signaling has been implicated in oncogenesis and tumor progression. EphA5 receptor is one of large families of Eph tyrosine kinase receptor and is documented in the development of nervous system. Till now, there is no published data about the role of EphA5 in ovarian epithelial neoplasmas.

Methods

This study aims to investigate the expression of EphA5 protein in ovarian serous carcinoma, and its relationship to clinical pathological characteristics. Sixty-one cases of ovarian serous carcinoma, 24 cases of benign ovarian serous tumors, 42 cases of serous borderline tumors and 20 cases of normal fallopian tubes were examined using immunohistochemical staining. The relationship between EphA5 expression and pathological parameters was analyzed. Kaplan-Meier survival function was used to analyze prognosis of patients.

Results

Immunostaining analysis demonstrated that the EphA5 protein was highly expressed in 100% (20/20) of normal fallopian tube samples, 100% (24/24) of benign epithelial ovarian tumors, 76% (32/42) of ovarian serous borderline tumors, and 31% (19/61) of ovarian serous carcinomas. Loss of EphA5expression was associated with tumor grade (P < 0.001) and FIGO stage (P = 0.005). The survival analysis showed that patients with negative or weak expression of EphA5 protein had a poor outcome than those with positive expression (P = 0.004).

Conclusions

Our results show that EphA5 may be a potential biomarker for distinguishing high-and low-grade ovarian serous carcinoma and a potential prognostic marker.
Literature
1.
go back to reference Cheon DJ, Tong Y, Sim MS, Dering J, Berel D, Cui X, et al. A collagen-remodeling gene signature regulated by TGF-beta signaling is associated with metastasis and poor survival in serous ovarian cancer. Clin Cancer Res. 2014;20(3):711–23.CrossRefPubMed Cheon DJ, Tong Y, Sim MS, Dering J, Berel D, Cui X, et al. A collagen-remodeling gene signature regulated by TGF-beta signaling is associated with metastasis and poor survival in serous ovarian cancer. Clin Cancer Res. 2014;20(3):711–23.CrossRefPubMed
2.
go back to reference Sherman-Baust CA, Kuhn E, Valle BL, Shih Ie M, Kurman RJ, Wang TL, et al. A genetically engineered ovarian cancer mouse model based on fallopian tube transformation mimics human high-grade serous carcinoma development. J Pathol. 2014;233(3):228–37.CrossRefPubMedPubMedCentral Sherman-Baust CA, Kuhn E, Valle BL, Shih Ie M, Kurman RJ, Wang TL, et al. A genetically engineered ovarian cancer mouse model based on fallopian tube transformation mimics human high-grade serous carcinoma development. J Pathol. 2014;233(3):228–37.CrossRefPubMedPubMedCentral
3.
go back to reference Faleiro-Rodrigues C, Macedo-Pinto I, Pereira D, Ferreira VM, Lopes CS. Association of E-cadherin and beta-catenin immunoexpression with clinicopathologic features in primary ovarian carcinomas. Hum Pathol. 2004;35(6):663–9.CrossRefPubMed Faleiro-Rodrigues C, Macedo-Pinto I, Pereira D, Ferreira VM, Lopes CS. Association of E-cadherin and beta-catenin immunoexpression with clinicopathologic features in primary ovarian carcinomas. Hum Pathol. 2004;35(6):663–9.CrossRefPubMed
4.
go back to reference Bhagat R, Premalata CS, Shilpa V, Pallavi VR, Ramesh G, Vijay CR, et al. Altered expression of beta-catenin, E-cadherin, and E-cadherin promoter methylation in epithelial ovarian carcinoma. Tumour Biol. 2013;34(4):2459–68.CrossRefPubMed Bhagat R, Premalata CS, Shilpa V, Pallavi VR, Ramesh G, Vijay CR, et al. Altered expression of beta-catenin, E-cadherin, and E-cadherin promoter methylation in epithelial ovarian carcinoma. Tumour Biol. 2013;34(4):2459–68.CrossRefPubMed
5.
go back to reference Vang R, Shih Ie M, Kurman RJ. Ovarian low-grade and high-grade serous carcinoma: pathogenesis, clinicopathologic and molecular biologic features, and diagnostic problems. Adv Anat Pathol. 2009;16(5):267–82.CrossRefPubMedPubMedCentral Vang R, Shih Ie M, Kurman RJ. Ovarian low-grade and high-grade serous carcinoma: pathogenesis, clinicopathologic and molecular biologic features, and diagnostic problems. Adv Anat Pathol. 2009;16(5):267–82.CrossRefPubMedPubMedCentral
6.
go back to reference O’Neill CJ, Deavers MT, Malpica A, Foster H, McCluggage WG. An immunohistochemical comparison between low-grade and high-grade ovarian serous carcinomas: significantly higher expression of p53, MIB1, BCL2, HER-2/neu, and C-KIT in high-grade neoplasms. Am J Surg Pathol. 2005;29(8):1034–41.PubMed O’Neill CJ, Deavers MT, Malpica A, Foster H, McCluggage WG. An immunohistochemical comparison between low-grade and high-grade ovarian serous carcinomas: significantly higher expression of p53, MIB1, BCL2, HER-2/neu, and C-KIT in high-grade neoplasms. Am J Surg Pathol. 2005;29(8):1034–41.PubMed
7.
go back to reference Numachi Y, Yoshida S, Yamashita M, Fujiyama K, Toda S, Matsuoka H, et al. Altered EphA5 mRNA expression in rat brain with a single methamphetamine treatment. Neurosci Lett. 2007;424(2):116–21.CrossRefPubMed Numachi Y, Yoshida S, Yamashita M, Fujiyama K, Toda S, Matsuoka H, et al. Altered EphA5 mRNA expression in rat brain with a single methamphetamine treatment. Neurosci Lett. 2007;424(2):116–21.CrossRefPubMed
8.
go back to reference Wu YJ, Xu MY, Wang L, Sun BL, Gu GX. Analysis of EphA5 receptor in the developing rat brain: an in vivo study in congenital hypothyroidism model. Eur J Pediatr. 2013;172(8):1077–83.CrossRefPubMed Wu YJ, Xu MY, Wang L, Sun BL, Gu GX. Analysis of EphA5 receptor in the developing rat brain: an in vivo study in congenital hypothyroidism model. Eur J Pediatr. 2013;172(8):1077–83.CrossRefPubMed
10.
go back to reference Yamada T, Yuasa M, Masaoka T, Taniyama T, Maehara H, Torigoe I, et al. After repeated division, bone marrow stromal cells express inhibitory factors with osteogenic capabilities, and EphA5 is a primary candidate. Bone. 2013;57(2):343–54.CrossRefPubMed Yamada T, Yuasa M, Masaoka T, Taniyama T, Maehara H, Torigoe I, et al. After repeated division, bone marrow stromal cells express inhibitory factors with osteogenic capabilities, and EphA5 is a primary candidate. Bone. 2013;57(2):343–54.CrossRefPubMed
11.
go back to reference Petkova TD, Seigel GM, Otteson DC. A role for DNA methylation in regulation of EphA5 receptor expression in the mouse retina. Vision Res. 2011;51(2):260–8.CrossRefPubMed Petkova TD, Seigel GM, Otteson DC. A role for DNA methylation in regulation of EphA5 receptor expression in the mouse retina. Vision Res. 2011;51(2):260–8.CrossRefPubMed
12.
go back to reference Caras IW. A link between axon guidance and axon fasciculation suggested by studies of the tyrosine kinase receptor EphA5/REK7 and its ligand ephrin-A5/AL-1. Cell Tissue Res. 1997;290(2):261–4.CrossRefPubMed Caras IW. A link between axon guidance and axon fasciculation suggested by studies of the tyrosine kinase receptor EphA5/REK7 and its ligand ephrin-A5/AL-1. Cell Tissue Res. 1997;290(2):261–4.CrossRefPubMed
13.
go back to reference St John JA, Tisay KT, Caras IW, Key B. Expression of EphA5 during development of the olfactory nerve pathway in rat. J Comp Neurol. 2000;416(4):540–50.CrossRefPubMed St John JA, Tisay KT, Caras IW, Key B. Expression of EphA5 during development of the olfactory nerve pathway in rat. J Comp Neurol. 2000;416(4):540–50.CrossRefPubMed
14.
go back to reference Fu DY, Wang ZM, Wang BL, Chen L, Yang WT, Shen ZZ, et al. Frequent epigenetic inactivation of the receptor tyrosine kinase EphA5 by promoter methylation in human breast cancer. Hum Pathol. 2010;41(1):48–58.CrossRefPubMed Fu DY, Wang ZM, Wang BL, Chen L, Yang WT, Shen ZZ, et al. Frequent epigenetic inactivation of the receptor tyrosine kinase EphA5 by promoter methylation in human breast cancer. Hum Pathol. 2010;41(1):48–58.CrossRefPubMed
15.
go back to reference Giaginis C, Tsourouflis G, Zizi-Serbetzoglou A, Kouraklis G, Chatzopoulou E, Dimakopoulou K, et al. Clinical significance of ephrin (eph)-A1, -A2, -a4, -a5 and -a7 receptors in pancreatic ductal adenocarcinoma. Pathol Oncol Res. 2010;16(2):267–76.CrossRefPubMed Giaginis C, Tsourouflis G, Zizi-Serbetzoglou A, Kouraklis G, Chatzopoulou E, Dimakopoulou K, et al. Clinical significance of ephrin (eph)-A1, -A2, -a4, -a5 and -a7 receptors in pancreatic ductal adenocarcinoma. Pathol Oncol Res. 2010;16(2):267–76.CrossRefPubMed
16.
go back to reference Gu Y, Li F, Qian N, Chen X, Wang H, Wang J. Expression of EphB6 in ovarian serous carcinoma is associated with grade, TNM stage and survival. J Clin Pathol. 2016;69(5):448-53. Gu Y, Li F, Qian N, Chen X, Wang H, Wang J. Expression of EphB6 in ovarian serous carcinoma is associated with grade, TNM stage and survival. J Clin Pathol. 2016;69(5):448-53.
17.
go back to reference Della Pepa C, Tonini G, Santini D, Losito S, Pisano C, Di Napoli M, et al. Low Grade Serous Ovarian Carcinoma: from the molecular characterization to the best therapeutic strategy. Cancer Treat Rev. 2015;41(2):136–43.CrossRefPubMed Della Pepa C, Tonini G, Santini D, Losito S, Pisano C, Di Napoli M, et al. Low Grade Serous Ovarian Carcinoma: from the molecular characterization to the best therapeutic strategy. Cancer Treat Rev. 2015;41(2):136–43.CrossRefPubMed
18.
go back to reference Bodurka DC, Deavers MT, Tian C, Sun CC, Malpica A, Coleman RL, et al. Reclassification of serous ovarian carcinoma by a 2-tier system: a Gynecologic Oncology Group Study. Cancer. 2012;118(12):3087–94.CrossRefPubMed Bodurka DC, Deavers MT, Tian C, Sun CC, Malpica A, Coleman RL, et al. Reclassification of serous ovarian carcinoma by a 2-tier system: a Gynecologic Oncology Group Study. Cancer. 2012;118(12):3087–94.CrossRefPubMed
19.
go back to reference Singh N, Ayhan A, Menon U, Chin Aleong JA, Faruqi AZ, Gayther SA, et al. Grading of serous ovarian carcinoma: further evidence of a lack of agreement between conventional grading systems. Histopathology. 2008;52(3):393–5.CrossRefPubMed Singh N, Ayhan A, Menon U, Chin Aleong JA, Faruqi AZ, Gayther SA, et al. Grading of serous ovarian carcinoma: further evidence of a lack of agreement between conventional grading systems. Histopathology. 2008;52(3):393–5.CrossRefPubMed
20.
21.
go back to reference Kober P, Bujko M, Oledzki J, Tysarowski A, Siedlecki JA. Methyl-CpG binding column-based identification of nine genes hypermethylated in colorectal cancer. Mol Carcinog. 2011;50(11):846–56.CrossRefPubMed Kober P, Bujko M, Oledzki J, Tysarowski A, Siedlecki JA. Methyl-CpG binding column-based identification of nine genes hypermethylated in colorectal cancer. Mol Carcinog. 2011;50(11):846–56.CrossRefPubMed
Metadata
Title
EphA5 protein, a potential marker for distinguishing histological grade and prognosis in ovarian serous carcinoma
Authors
Xiao Chen
Xuan Wang
Xue Wei
Jiandong Wang
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2016
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-016-0292-1

Other articles of this Issue 1/2016

Journal of Ovarian Research 1/2016 Go to the issue