Canonical and noncanonical Wnt pathways: a comparison between endometrial cancer type I and atrophic endometrium in Brazil.

Marina De Pádua Nogueira Menezes,Wagner José Gonçalves,Celina Tizuko Fujiyama Oshima,Levon Badiglian Filho,Thiago Simão Gomes,Luis Fernando Mesias Barrezueta,João Norberto Stávale

doi:10.1590/s1516-31802011000500007

Marina De Pádua Nogueira Menezes, Wagner José Gonçalves + Show 5 more

Open Access

https://doi.org/10.1590/s1516-31802011000500007

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Abstract

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. Cross-sectional study on materials gathered from the tissue bank of the Department of Pathology, Universidade Federal de São Paulo. 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. 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). FZD5 is downregulated in endometrial adenocarcinoma, in comparison with atrophic endometrium.

Highlights

The Wnt family has an important role in tumorigenesis and embryogenesis.[1,2,3,4,5] Wnts are an evolutionarily highly conserved family of genes/proteins that act through three signaling pathways.[6]
The proportion of FZD5-positive women was significantly higher in group A (80.0%) than in group B (31.1%)
Canonical pathway Endometrioid endometrial adenocarcinoma is essentially connected with type I endometrial cancer, which in turn correlates with hyperestrogenism status

Summary

Introduction

The Wnt family has an important role in tumorigenesis and embryogenesis.[1,2,3,4,5] Wnts are an evolutionarily highly conserved family of genes/proteins that act through three signaling pathways.[6] The canonical pathway involves regulation of betacatenin. In the absence of Wnt signaling, a multiprotein complex that includes adenomatous polyposis coli (APC), glycogen synthase kinase-3 (GSK3) and axin ensures degradation of beta-catenin, thereby limiting the free intracytoplasmic pool of beta-catenin. The presence of Wnt signaling through the Frizzled (FZD) receptor and the low-density lipoprotein receptor-related protein 5 and 6 (LRP5/6) receptor complex inactivates GSK3 and causes its dissociation from axin, thereby preventing phosphorylation of beta-catenin. The intracytoplasmic pool of beta-catenin increases, and it translocates to the nucleus, where it complexes with members of the T-cell factor/lymphocyte enhancement factor (LEF/TCF) family of transcription factors to mediate transcriptional induction of target genes such as c-myc, cyclin D, vascular endothelial growth factor (VEGF) and others.[1,2,3,4,5]

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