Skip to main content
Erschienen in: Tumor Biology 4/2013

01.08.2013 | Research Article

Altered expression of β-catenin, E-cadherin, and E-cadherin promoter methylation in epithelial ovarian carcinoma

verfasst von: Rahul Bhagat, C. S. Premalata, V. Shilpa, V. R. Pallavi, G. Ramesh, C. R. Vijay, Lakshmi Krishnamoorthy

Erschienen in: Tumor Biology | Ausgabe 4/2013

Einloggen, um Zugang zu erhalten

Abstract

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.
Literatur
1.
Zurück zum Zitat Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedCrossRef Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedCrossRef
2.
3.
Zurück zum Zitat 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. 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.
4.
Zurück zum Zitat Shiozaki H, Oka H, Inoue M, Tamura S, Monden ME. cadherin mediated adhesion system in cancer cells. Cancer. 1996;77:1605–13. 1540.PubMed Shiozaki H, Oka H, Inoue M, Tamura S, Monden ME. cadherin mediated adhesion system in cancer cells. Cancer. 1996;77:1605–13. 1540.PubMed
5.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
7.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
8.
Zurück zum Zitat 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.PubMed 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.PubMed
9.
Zurück zum Zitat Nelson WJ, Nusse R. Convergence of Wnt, β-catenin, and cadherin pathways. Science. 2004;303:1483–7.PubMedCrossRef Nelson WJ, Nusse R. Convergence of Wnt, β-catenin, and cadherin pathways. Science. 2004;303:1483–7.PubMedCrossRef
10.
Zurück zum Zitat 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 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
11.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
12.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
13.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
14.
Zurück zum Zitat 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.PubMed 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.PubMed
15.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
16.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
17.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
18.
Zurück zum Zitat 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.PubMed 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.PubMed
19.
Zurück zum Zitat 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.PubMed 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.PubMed
20.
Zurück zum Zitat Hirohashi S. Inactivation of the E-cadherin-mediated cell adhesion system in human cancers. Am J Pathol. 1998;153:333–9.PubMedCrossRef Hirohashi S. Inactivation of the E-cadherin-mediated cell adhesion system in human cancers. Am J Pathol. 1998;153:333–9.PubMedCrossRef
21.
Zurück zum Zitat 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.PubMed 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.PubMed
22.
Zurück zum Zitat 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 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
23.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
24.
25.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
26.
Zurück zum Zitat 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.PubMed 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.PubMed
27.
Zurück zum Zitat 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.PubMed 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.PubMed
28.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
29.
Zurück zum Zitat 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. 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.
30.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
31.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
32.
Zurück zum Zitat 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.PubMed 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.PubMed
33.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
34.
Zurück zum Zitat 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. 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.
35.
Zurück zum Zitat 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 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
36.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
37.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
38.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
39.
Zurück zum Zitat 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.PubMed 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.PubMed
40.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
41.
Zurück zum Zitat 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.PubMed 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.PubMed
Metadaten
Titel
Altered expression of β-catenin, E-cadherin, and E-cadherin promoter methylation in epithelial ovarian carcinoma
verfasst von
Rahul Bhagat
C. S. Premalata
V. Shilpa
V. R. Pallavi
G. Ramesh
C. R. Vijay
Lakshmi Krishnamoorthy
Publikationsdatum
01.08.2013
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 4/2013
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-0797-9

Weitere Artikel der Ausgabe 4/2013

Tumor Biology 4/2013 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.