Study of Beta-Catenin Expression: In Endometrial Hyperplasia and Carcinoma
Keywords:
beta-catenin, proliferative endometrium, atypical hyperplasia, endometrial carcinoma
Abstract
Background: Beta-catenin is normally expressed in the membrane and cytoplasm of endometrial glandular cells. Aberrations in beta-catenin expression can predict progression of endometrial hyperplasia to endometrial carcinoma. Nuclear expression of beta-catenin correlates with the increasing histological grade of endometrial cancer. Methods: 51 cases were included in our study. The patients presented with clinical and/or radiological evidence of probable endometrial disease. Formalin fixed paraffin embedded tissues were stained with hematoxylin and eosin followed by histological diagnosis and exact categorisation. Immunostaining with anti-beta-catenin monoclonal antibody carried out on these endometrial biopsies. Result: Statistically significant association was seen between nuclear positivity of beta-catenin in the endometrial glandular cells with increasing severity of endometrial pathology (P < 0.001). Atypical hyperplasia and endometrial carcinoma cases showed nuclear beta-catenin positivity. Nuclear expression of beta-catenin also correlated with advanced FIGO stage of endometrial carcinomas. 67% of endometrial carcinoma of FIGO stage III demonstrated nuclear localization of beta-catenin. A statistically significant association was noted between the intensity of beta-catenin expression and the histological diagnosis (P < 0.001). There was also a statistically significant association between percentage of endometrial glandular cells showing membranous and cytoplasmic positivity and the endometrial pathology (P=0.038). Conclusion: Variations in beta-catenin expression play an important role in endometrial pathology and it is a relatively early event during the endometrial hyperplasia-carcinoma sequence. Alterations in beta-catenin expression in atypical endometrial hyperplasia and in increasing grades of endometrial cancers can be used as a predictive as well as a prognostic indicator.References
[1] Kurman RJ, Ellenson LH, Ronnett BM. Precursor Lesions of Endometrial Carcinoma. In: Kurman RJ, editor. Blaustein’s Pathology of the Female Genital Tract. Sixth Edition. New York: Springer; 2011:360.
[2] Okuda T, Sekizawa A, Purwosunu Y et al. Genetics of Endometrial Cancers. Hindawi Publishing Corporation Obstetrics and Gynecology International. 2010; 2010: 8 pages.
[3] Hendrickson MR, Longacre TA, Kempson RL. Female Reproductive System and Peritoneum. In: Sternberg's Diagnostic Surgical Pathology. Fifth Edition. Philadelphia: Wolters Kluwer Health; 2015. 2204.
[4] Jiang WG. E-cadherin and its associated protein catenins, cancer invasion and metastasis. Br J Surg. 1996; 83. 437-46.
[5] Gumbiner BM. Cell adhesion: The Molecular Basis of Tissue Architecture and Morphogenesis. Cell. 1996; 84. 345-57.
[6] Provost E, Rimm DL. Controversies at the cytoplasmic face of the cadherin-based adhesion complex. Curr Opin Cell Biol. 1999; 11 (5). 567-72.
[7] Shih HC, Shiozawa T, Miyamoto T et al. Immunohistochemical Expression of E-cadherin and beta-catenin in the Normal and Malignant Human Endometrium: An Inverse Correlation between E-cadherin and Nuclear beta-catenin Expression. Anticancer Research. 2004; 24. 3843-50.
[8] Bueno GM, Hardisson D, Sanchez C, Sarrio D, Cassia R, Prat J. Abnormalities of the APC/beta-catenin pathway in endometrial cancer. Oncogene. 2002; 21. 7981 – 90.
[9] Xiong Y, Xiong YY, Zhou YF. Expression of beta-catenin, Glut-1, PTEN proteins in uterine endometrioid adenocarcinoma and its precursor lesions. Zhonghua Bing Li Xue Za Zhi. 2009; 38(9). 594-9.
[10] Scholten AN, Creutzberg CL, van den Broek L, Noordijk EM, Smit VT. Nuclear beta-catenin is a molecular feature of type I endometrial carcinoma. J Pathol. 2003; 201(3). 460-5.
[11] Mc Crea PD, Turck CW, Gumbiner B. A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin. Science. 1991; 254 (5036). 1359–61.
[12] Kemler R. From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion. Trends Genet. 1993; 9 (9). 317–21.
[13] Saegusa M, Hashimura M, Yoshida T, Okayasu I. Beta-catenin mutations and aberrant nuclear expression during endometrial tumorigenesis. Br J Cancer. 2001; 84. 209-17.
[2] Okuda T, Sekizawa A, Purwosunu Y et al. Genetics of Endometrial Cancers. Hindawi Publishing Corporation Obstetrics and Gynecology International. 2010; 2010: 8 pages.
[3] Hendrickson MR, Longacre TA, Kempson RL. Female Reproductive System and Peritoneum. In: Sternberg's Diagnostic Surgical Pathology. Fifth Edition. Philadelphia: Wolters Kluwer Health; 2015. 2204.
[4] Jiang WG. E-cadherin and its associated protein catenins, cancer invasion and metastasis. Br J Surg. 1996; 83. 437-46.
[5] Gumbiner BM. Cell adhesion: The Molecular Basis of Tissue Architecture and Morphogenesis. Cell. 1996; 84. 345-57.
[6] Provost E, Rimm DL. Controversies at the cytoplasmic face of the cadherin-based adhesion complex. Curr Opin Cell Biol. 1999; 11 (5). 567-72.
[7] Shih HC, Shiozawa T, Miyamoto T et al. Immunohistochemical Expression of E-cadherin and beta-catenin in the Normal and Malignant Human Endometrium: An Inverse Correlation between E-cadherin and Nuclear beta-catenin Expression. Anticancer Research. 2004; 24. 3843-50.
[8] Bueno GM, Hardisson D, Sanchez C, Sarrio D, Cassia R, Prat J. Abnormalities of the APC/beta-catenin pathway in endometrial cancer. Oncogene. 2002; 21. 7981 – 90.
[9] Xiong Y, Xiong YY, Zhou YF. Expression of beta-catenin, Glut-1, PTEN proteins in uterine endometrioid adenocarcinoma and its precursor lesions. Zhonghua Bing Li Xue Za Zhi. 2009; 38(9). 594-9.
[10] Scholten AN, Creutzberg CL, van den Broek L, Noordijk EM, Smit VT. Nuclear beta-catenin is a molecular feature of type I endometrial carcinoma. J Pathol. 2003; 201(3). 460-5.
[11] Mc Crea PD, Turck CW, Gumbiner B. A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin. Science. 1991; 254 (5036). 1359–61.
[12] Kemler R. From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion. Trends Genet. 1993; 9 (9). 317–21.
[13] Saegusa M, Hashimura M, Yoshida T, Okayasu I. Beta-catenin mutations and aberrant nuclear expression during endometrial tumorigenesis. Br J Cancer. 2001; 84. 209-17.
Published
2018-07-20
Issue
Section
Original Article
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access at http://opcit.eprints.org/oacitation-biblio.html).
