Altered expression of β-catenin, E-cadherin, and E-cadherin promoter methylation in epithelial ovarian carcinoma
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
The aim of the study was to evaluate the immunoexpression of E-cadherin, β-catenin, and Ki-67, as well as the promoter methylation of E-cadherin gene in epithelial ovarian cancer (EOC), as well as to find a possible relationship between the immunoexpression and hypermethylation. Promoter methylation was studied using methylation-specific PCR in 86 malignant cases, 14 low malignant potential (LMP) tumors and 19 benign cystadenomas. Immunohistochemical expression was carried out in 64 malignant cases, 8 LMP tumors, and 11 benign cystadenomas. Immunoexpression of E-cadherin was reduced in EOC, while 100 % expression was seen in LMP tumors and benign cystadenomas. An interesting observation was the nuclear expression of E-cadherin in a high percentage of cancers, which showed a positive correlation with Ki-67. Β-Catenin expression showed heterogeneous localization with increased nuclear localization, which was significantly higher in cases that did not express E-cadherin. Promoter methylation of E-cadherin was 36, 14, and 11 % in EOC, LMP tumors, and benign cystadenomas, respectively. Our results suggest that reduced expression of E-cadherin is associated with promoter methylation of E-cadherin gene, in addition to providing evidence for the aberrant nuclear localization of E-cadherin in EOC.
- Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108. CrossRef
- Jemal A, Thomas A, Murray T. Cancer statistics, 2002. CA Cancer J Clin. 2002;52:23–47. CrossRef
- Ozols RF, Rubin SC, Thomas GM Robboy SJ. Epithelial ovarian cancer. In: Hoskins WJ, Perez CA, Young RC, editors. Principles and practice of gynecologic oncology, 3rd edition. Philadelphia: Lippincott, Williams & Wilkins; 2000. p. 981–1058.
- Shiozaki H, Oka H, Inoue M, Tamura S, Monden ME. cadherin mediated adhesion system in cancer cells. Cancer. 1996;77:1605–13. 1540.
- Gervais ML, Henry PC, Saravanan A, Burry TN, Gallie BL, Jewett MA, et al. Nuclear E-cadherin and VHL immunoreactivity are prognostic indicators of clear-cell renal cell carcinoma. Lab Invest. 2007;87:1252–64. CrossRef
- Meyer T, Hart IR. Mechanisms of tumour metastasis. Eur J Cancer. 1998;34:214–21. CrossRef
- Karim R, Tse G, Putti T, Scolyer R, Lee S. The significance of the Wnt pathway in the pathology of human cancers. Pathology. 2004;36:120–8. CrossRef
- Aberle H, Butz S, Stappert J, Weissig H, Kemler R, Hoschuetzky H. Assembly of the cadherin-catenin complex in vitro with recombinant proteins. J Cell Sci. 1994;107(Pt 12):3655–63.
- Nelson WJ, Nusse R. Convergence of Wnt, β-catenin, and cadherin pathways. Science. 2004;303:1483–7. CrossRef
- Faleiro-Rodrigues C, Macedo-Pinto IM, Maia SS, Vieira RH, Lopes CS. Biological relevance of E-cadherin-catenin complex proteins in primary epithelial ovarian tumors. Gynecol Obstet Invest. 2005;2:75–83. CrossRef
- Chen HC, Chu RY, Hsu PN, Hsu PI, Lu JY, Lai KH, et al. Loss of E-cadherin expression correlates with poor differentiation and invasion into adjacent organs in gastric adenocarcinomas. Cancer Lett. 2003;201:97–106. CrossRef
- Koksal IT, Ozcan F, Kilicaslan I, Tefekli A. Expression of E-cadherin in prostate cancer in formalin-fixed, paraffin-embedded tissues: correlation with pathological features. Pathology. 2002;34:233–8. CrossRef
- Kanazawa T, Watanabe T, Kazama S, Tada T, Koketsu S, Nagawa H. Poorly differentiated adenocarcinoma and mucinous carcinoma of the colon and rectum show higher rates of loss of heterozygosity and loss of E-cadherin expression due to methylation of promoter region. Int J Cancer. 2002;102:225–9. CrossRef
- Yoshida R, Kimura N, Harada Y, Ohuchi N. The loss of E-cadherin, a and b-catenin expression is associated with metastasis and poor prognosis in invasive breast cancer. Int J Oncol. 2001;18:513–20.
- Gonzalez MA, Pinder SE, Wencyk PM, Bell JA, Elston CW, Nicholson RI, et al. An immunohistochemical examination of the expression of E-cadherin, alpha- and beta/gamma-catenins, and alpha2- and beta1-integrins in invasive breast cancer. J Pathol. 1999;187:523–9. CrossRef
- Gillett CE, Miles DW, Ryder K, Skilton D, Liebman RD, Springall RJ, et al. Retention of the expression of E-cadherin and catenins is associated with shorter survival in grade III ductal carcinoma of the breast. J Pathol. 2001;193:433–41. CrossRef
- Tan DS, Potts HW, Leong AC, Gillett CE, Skilton D, Harris WH, et al. The biological and prognostic significance of cell polarity and E-cadherin in grade I infiltrating ductal carcinoma of the breast. J Pathol. 1999;189:20–7. CrossRef
- Kase S, Sugio K, Yamazaki K, Okamoto T, Yano T, Sugimachi K. Expression of E-cadherin and beta-catenine in human non-small cell lung cancer and the clinical significance. Clin Cancer Res. 2000;6:4789–96.
- Gofuku J, Shiozaki H, Tsujinaka T, Inoue M, Tamura S, Doki Y, et al. Expression of E-cadherin and alpha-catenine in patients with colorectal carcinoma. Correlation with cancer invasion and metastasis. Am J Clin Pathol. 1999;111:29–37.
- Hirohashi S. Inactivation of the E-cadherin-mediated cell adhesion system in human cancers. Am J Pathol. 1998;153:333–9. CrossRef
- Birchmeier W, Behrens J. Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta. 1994;1198:11–26.
- Ba´nkfalvi A, Krabort M, Buchwalow VA, Vegh A, Felszeghy E, Piffko J. Gains and losses of adhesion molecules (CD44, E-cadherin, b-catenin) during oral carcinogenesis and tumour progression. J Pathol. 2002;198:343–51. CrossRef
- Katagiri A, Watanabe R, Tomita Y. E-Cadherin expression in renal cell cancer and its significance in metastasis and survival. Br J Cancer. 1995;71:376–9. CrossRef
- Xu L, Jiang Y, Zheng J, Xie G, Li J, Shi L, et al. Aberrant expression of β-catenin and E-cadherin is correlated with poor prognosis of nasopharyngeal cancer. Hum Pathol. 2013. doi:10.1016/j.humpath.2012.10.025.
- Krishnadath KK, Tilanus HW, van Blankenstein M, Hop WC, Kremers ED, Dinjens WN, et al. Reduced expression of the cadherin–catenin complex in oesophageal adenocarcinoma correlates with poor prognosis. J Pathol. 1997;182:331–8. CrossRef
- Han AC, Soler AP, Tang CK, Knudsen KA, Salazar H. Nuclear localization of E-cadherin expression in Merkel cell carcinoma. Arch Pathol Lab Med. 2000;124:1147–51.
- Moon KC, Cho SY, Lee HS, Jeon YK, Chung JH, Jung KC, et al. Distinct expression patterns of E-cadherin and beta-catenin in signet ring cell carcinoma components of primary pulmonary adenocarcinoma. Arch Pathol Lab Med. 2006;130:1320–5.
- Cespedes MV, Larriba MJ, Paron MA, Alamo P, Casanova I, Parreno M, et al. Site- dependent E-cadherin cleavage and nuclear translocation in metastatic colorectal cancer model. Am J Pathol. 2010;177(4):2067–79. CrossRef
- Serra S, Salahshor S, Fagih M, Niakosari F, Radhi JM, Chetty R. Nuclear expression of E-cadherin in solid pseudopapillary tumours of the pancreas. J Pancreas. 2007;8:296–303.
- Ferber EC, Kajita M, Wadlow A, Tobiansky L, Niessen C, Ariga H, et al. A role for the cleaved cytoplasmic domain of E-cadherin in the nucleus. J Biol Chem. 2008;283:12691–700. CrossRef
- Salahshor S, Naidoo R, Serra S, Shih W, Tsao MS, Chetty R, et al. Frequent accumulation of nuclear E-cadherin and alterations in the Wnt signaling pathway in esophageal squamous cell carcinomas. Mod Pathol. 2008;21:271–81. CrossRef
- Hashimoto T, Yanaihara N, Okamoto A, Nikaido T, Saito M, Takakura S, et al. Cyclin D1 predicts the prognosis of advanced serous ovarian cancer. Exp Ther Med. 2011;2(2):213–9.
- Ishida K, Ito S, Wada N, Deguchi H, Hata T, Hosoda M, et al. Nuclear localization of beta-catenin involved in precancerous change in oral leukoplakia. Mol Cancer. 2007;6:62. CrossRef
- Faleiro-Rodriquez C, Macedo-Pinto I. Association of E-cadherin and beta-catenin immunoexpression with clinicopathologic features in primary ovarian carcinomas. Hum Pathol. 2004;6:647–8.
- Xiao L, Yu L, Can M. Expression of beta-catenin and APC protein in ovarian epithelial tumor and its implication. Chin J Canc Res. 2007;19:72–5. CrossRef
- Sakuragi N, Nishiya M, Ikeda K, Ohkouch T, Furth EE, Hareyama H, et al. Decreased E-cadherin expression in endometrial carcinoma is associated with tumor dedifferentiation and deep myometrial invasion. Gynecol Oncol. 1994;53:183–9. CrossRef
- Cleton-Jansen AM. E-cadherin and loss of heterozygosity at chromosome 16 in breast carcinogenesis: different genetic pathways in ductal and lobular breast cancer? Breast Cancer Res. 2002;4:5–8. CrossRef
- Park SY, Kim BH, Kim JH, Cho NY, Choi M, Yu EJ, et al. Methylation profiles of CpG island loci in major types of human cancers. J Korean Med Sci. 2007;22:311–7. CrossRef
- Young C-H, Chiu Y-T, Shih T-S, Lin W-R, Chiang C-C, Chou Y-E. E-cadherin promoter methylation may contribute to protein inactivation in pterygia. Mol Vis. 2010;16:1047–53.
- Makarla PB, Saboorian MH, Ashfaq R, Toyooka KO, Toyooka S, Minna JD, et al. Promoter hypermethylation profile of ovarian epithelial neoplasms. Clin Cancer Res. 2005;11:5365–9. CrossRef
- Rathi A, Virmani AK, Schorge JO, Elias KJ, Maruyama R, Minna JD, et al. Methylation profiles of sporadic ovarian tumors and nonmalignant ovaries from high-risk women. Clin Cancer Res. 2002;8:3324–31.
- Altered expression of β-catenin, E-cadherin, and E-cadherin promoter methylation in epithelial ovarian carcinoma
Volume 34, Issue 4 , pp 2459-2468
- Cover Date
- Print ISSN
- Online ISSN
- Springer Netherlands
- Additional Links
- Promoter methylation
- LMP tumors
- Author Affiliations
- 1. Department of Biochemistry, Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda Road, Bangalore, 560029, India
- 2. Department of Pathology, Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda Road, Bangalore, 560029, India
- 3. Department of Epidemiology & Biostatistics, Kidwai Memorial Institute of Oncology, Dr. M.H. Marigowda Road, Bangalore, 560029, India