Canonical and noncanonical Wnt pathways
a comparison between endometrial cancer type I and atrophic endometrium in Brazil
Keywords:
Wnt proteins, Endometrial neoplasms, Women, Postmenopause, EndometriumAbstract
CONTEXT AND OBJECTIVE: The Wnt pathway is involved in tumorigenesis of several tissues. For this reason, we proposed to evaluate Wnt gene expression in endometrial cancer type I. DESIGN AND SETTING: Cross-sectional study on materials gathered from the tissue bank of the Department of Pathology, Universidade Federal de São Paulo. METHODS: Endometrial specimens were obtained from surgeries performed between 1995 and 2005 at São Paulo Hospital, Universidade Federal de São Paulo. The material was divided into two groups according to tissue type: Group A, atrophic endometrium (n = 15); and Group B, endometrial adenocarcinoma (n = 45). We compared the immunohistochemical expression of Wnt1, Frizzled-1 (FZD1), Wnt5a, Frizzled-5 (FZD5) and beta-catenin between endometrial cancer type I and atrophic endometrium. RESULTS: Regarding Wnt1, FZD1 and Wnt5a expression, no significant association was observed between the groups. A significant association was observed between the groups in relation to FZD5 expression (P = 0.001). The proportion of FZD5-positive samples was significantly higher in group A (80.0%) than in group B (31.1%). Regarding the survival curve for FZD5 in group B, we did not find any significant association between atrophic endometrium and endometrial adenocarcinoma. We also did not find any significant association regarding beta-catenin expression (P = 1.000). CONCLUSION: FZD5 is downregulated in endometrial adenocarcinoma, in comparison with atrophic endometrium.
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References
Fukuchi T, Sakamoto M, Tsuda H, et al. Beta-catenin mutation in carcinoma of the uterine endometrium. Cancer Res. 1998;58(16):3526-8.
Schlosshauer PW, Pirog EC, Levine RL, Ellenson LH. Mutational analysis of the CTNNB1 and APC genes in uterine endometrioid carcinoma. Mod Pathol. 2000;13(10):1066-71.
Pijnenborg JM, Kisters N, van Engeland M, et al. APC, beta-catenin, and E-cadherin and the development of recurrent endometrial carcinoma. Int J Gynecol Cancer. 2004;14(5):947-56.
Kariola R, Abdel-Rahman WM, Ollikainen M, et al. APC and beta- catenin protein expression patterns in HNPCC-related endometrial and colorectal cancers. Fam Cancer. 2005;4(2):187-90.
Schlosshauer PW, Ellenson LH, Soslow RA. Beta-catenin and E-cadherin expression patterns in high-grade endometrial carcinoma are associated with histological subtype. Mod Pathol. 2002;15(10):1032-7.
Bansal N, Yendluri V, Wenham RM. The molecular biology of endometrial cancers and the implications for pathogenesis, classification, and targeted therapies. Cancer Control. 2009;16(1):8-13.
Wappenschmidt B, Wardelmann E, Gehrig A, et al. PTEN mutations do not cause nuclear beta-catenin accumulation in endometrial carcinomas. Hum Pathol. 2004;35(10):1260-5.
Nei H, Saito T, Yamasaki H, et al. Nuclear localization of beta- catenin in normal and carcinogenic endometrium. Mol Carcinog. 1999;25(3):207-18.
Pecorelli S, Ngan HYN, Hacker NF. Staging Classifications and Clinical Practice Guidelines for Gynaecological Cancers. Available from: http:// www.figo.org/files/figo-corp/docs/staging_booklet.pdf. Accessed in 2011 (May 12).
Hou X, Tan Y, Li M, Dey SK, Das SK. Canonical Wnt signaling is critical to estrogen-mediated uterine growth. Mol Endocrinol. 2004;18(12):3035-49.
Kouzmenko AP, Takeyama K, Ito S, et al. Wnt/beta-catenin and estrogen signaling converge in vivo. J Biol Chem. 2004;279(39):40255-8.
Zhang Q, Shen Q, Celestino J, et al. Enhanced estrogen-induced proliferation in obese rat endometrium. Am J Obstet Gynecol. 2009;200(2):186.e1-8.
Ishitani T, Kishida S, Hyodo-Miura J, et al. The TAK1-NLK mitogen- activated protein kinase cascade functions in the Wnt-5a/Ca(2+) pathway to antagonize Wnt/beta-catenin signaling. Mol Cell Biol. 2003;23(1):131-9.
Topol L, Jiang X, Choi H, et al. Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent beta-catenin degradation. J Cell Biol. 2003;162(5):899-908.
Singleton DW, Feng Y, Yang J, et al. Gene expression profiling reveals novel regulation by bisphenol-A in estrogen receptor-alpha-positive human cells. Environ Res. 2006;100(1):86-92.
Jönsson M, Dejmek J, Bendahl PO, Andersson T. Loss of Wnt-5a protein is associated with early relapse in invasive ductal breast carcinomas. Cancer Res. 2002;62(2):409-16.
Fernandez-Cobo M, Zammarchi F, Mandeli J, Holland JF, Pogo BG. Expression of Wnt5A and Wnt10B in non-immortalized breast cancer cells. Oncol Rep. 2007;17(4):903-7.
Benhaj K, Akcali KC, Ozturk M. Redundant expression of canonical Wnt ligands in human breast cancer cell lines. Oncol Rep. 2006;15(3):701-7.
Badiglian Filho L, Oshima CT, De Oliveira Lima F, et al. Canonical and noncanonical Wnt pathway: a comparison among normal ovary, benign ovarian tumor and ovarian cancer. Oncol Rep. 2009;21(2):313-20.
Bui TD, Zhang L, Rees MC, Bicknell R, Harris AL. Expression and hormone regulation of Wnt2, 3, 4, 5a, 7a, 7b and 10b in normal human endometrium and endometrial carcinoma. Br J Cancer. 1997;75(8):1131-6.
