Endometrial carcinoma: pathology and genetics

Prat, Jaime; Gallardo, Alberto; Cuatrecasas, Míriam; Catasús, Lluis

doi:10.1080/00313020601136153

Cited by 174 publications

(169 citation statements)

References 150 publications

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“…Patients often have postmenopausal uterine bleeding (Acmaz et al, 2014) that help to diagnos in early stages, and those with stage I EC have a survival rate of over 90% (Cetinkaya et al, 2014) however, stage III patients have a 5-year survival rate of around 60-75% (Neubauer and Lurain, 2011). Approximately 90% of endometrial cancers are sporadic, and 10% of them are hereditary (Prat et al, 2007). More than half of all cancer cases and deaths worldwide are potentially preventable (Zeng et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

The Polymorphism of Hypoxia-inducible Factor-1a Gene in Endometrial Cancer

Kafshdooz¹,

Tabrizi²,

Mohaddes³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: Endometral carcinoma is the most common malignant tumor of the female genital tract and the fourth most common cancer in women after breast, colorectal and lung cancers Hypoxia-inducible factor -1 (HIF-1) is a key transcription factor that regulates cellular response to hypoxia HIF-1 plays important roles in the development and progression of cancer through activation of various genes that are involved in crucial aspects of cancer biology, including angiogenesis, energy metabolism, vasomotor function, erythropoiesis, and cell survival. In this study, we aimed to investigate the association between HIF-1 1772 C/T polymorphisms and endometrial cancer. Materials and Methods: 75 patients with endometrial carcinoma and 75 patients whose underwent hysterectomy for non tumoral indication selected for evaluation of HIF-1 1772 C/T polymorphisms by PCR-RFLP and sequencing. Results: For the 1772 C/T polymorphism, the analysis showed that the T allele and genotype TT were significantly associated with endometrial cancer risk. Conclusions: Our results suggest that the C1772T polymorphism of the HIF-1a may be associated with endometrial cancers.

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Section: Introductionmentioning

confidence: 99%

The Polymorphism of Hypoxia-inducible Factor-1a Gene in Endometrial Cancer

Kafshdooz¹,

Tabrizi²,

Mohaddes³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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“…More recently, studies have linked the β-catenin/ canonical Wnt signaling pathway to disease onset and tumorogenesis [11][12][13]. The development of cancer has been attributed to mutations resulting in constitutive activation of *Corresponding Author: Phone: 713-500-7440, Fax: 713-500-7455, David.S.Loose@uth.tmc.edu.…”

Section: Introductionmentioning

confidence: 99%

Wnt7a interaction with Fzd5 and detection of signaling activation using a split eGFP

Carmon

Loose

2008

Biochemical and Biophysical Research Communications

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Wnts are secreted glycoproteins that regulate important cellular processes including proliferation, diiferentiation, and cell fate. In the β-catenin/canonical pathway, Wnt interacts with Fzd receptors to inhibit degradation of β-catenin and promote its translocation into the nucleus where it regulates transcription of a number of genes. Dysregulation of this pathway has been attributed to a host of diseases including cancer. As a result, components of the β-catenin/canonical pathway have been gaining recognition as promising targets for the discovery of novel therapeutic agents. Here we show, using an ELISA-based protein-protein binding assay that purified Wnt7a binds to the extracellular cysteine-rich domain of Fzd5 in the nanomolar range. We have developed a novel split eGFP complementation assay to visually detect Wnt7a-Fzd5 interactions and subsequent pathway activation in cells. These biological tools could help lead to a better understanding of Wnt-Fzd interactions and the identification of new modulators of Wnt signaling. KeywordsWnt signaling; Wnt7a; Fzd5; split eGFP; protein complementationThe β-catenin/canonical Wnt pathway defines a series of events that occur when Wnt proteins bind to cell-surface receptors of the Frizzled (Fzd) family. Currently, 19 Wnt proteins and 10 different Fzd members have been identified in the human genome[1;2]. The Wnt-Fzd interaction promotes complex formation with a membrane-associated Lrp 5/6 co-receptor and activates signaling through the direct recruitment of a Dishevelled (Dsh) protein to the intracellular portion of Fzd[3;4]. Dsh inhibits GSK-3 association with the Axin/APC complex of proteins that normally mark β-catenin for proteolytic degradation [5]. Intracellular pools of cytoplasmic β-catenin become stabilized, enter into the nucleus, and interact with the TCF/ LEF family of transcription factors to promote specific gene expression [6;7]. The Wnt-Fzd interaction has also been shown to activate two distinct non-canonical pathways; the planar cell polarity/JNK pathway and a Ca 2+ -mediated pathway[2;8;9].Wnt was initially discovered as a proto-oncogene in mammary tumors activated by integration of the mouse mammary tumor virus [10]. More recently, studies have linked the β-catenin/ canonical Wnt signaling pathway to disease onset and tumorogenesis [11][12][13]. The development of cancer has been attributed to mutations resulting in constitutive activation of *Corresponding Author: Phone: 713-500-7440, Fax: 713-500-7455, David.S.Loose@uth.tmc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Me...

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“…1 Two main types have been recognized: 2 type I are endometrioid adenocarcinomas, which represent B80% of endometrial carcinomas. 3 They develop in peri-or post-menopausal women and are related to estrogen stimulation. They are predominantly low-grade endometrioid adenocarcinomas, often confined to the uterus and are frequently preceded by endometrial hyperplasia.…”

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confidence: 99%

Concomitant PI3K–AKT and p53 alterations in endometrial carcinomas are associated with poor prognosis

et al. 2009

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The status of p53 and the phosphatidylinositol 3-kinase-AKT (PI3K-AKT) signaling pathway was investigated in 132 endometrial carcinomas, including endometrioid endometrial carcinomas, non-endometrioid endometrial carcinomas, and mixed endometrioid adenocarcinomas-non-endometrioid adenocarcinomas. Results were compared with the clinicopathologic parameters associated with prognosis, patients' follow-up, and other genetic alterations found frequently in these tumors. Molecular genetic differences between low-grade and high-grade endometrioid adenocarcinomas were encountered; ie, PIK3CA mutations were detected in 26 and 34% of cases, respectively. We found p53 alterations in only 17% of high-grade endometrioid adenocarcinomas. In contrast, non-endometrioid adenocarcinomas had a higher frequency of p53 alterations (54%), PIK3CA mRNA overexpression (45%), and exon 20 PIK3CA mutations (21%). In the mixed endometrioid adenocarcinomas-non-endometrioid adenocarcinomas, the most frequent alterations were p53 (50%) and PIK3CA (44%) mutations, followed by PTEN mutations (38%). In some cases, p53 and PIK3CA alterations coexisted, but they rarely coexisted with the PTEN mutations. Our findings suggest that the PIK3CA mutations are frequent events in endometrial carcinomas of any histological type. However, location of the PIK3CA mutations, either in exon 9 or exon 20, varies significantly according to the histologic grade and type of carcinoma. Carcinomas with exon 20 PIK3CA mutations or PIK3CA mRNA overexpression were often high-grade carcinomas associated with myometrial invasion; in contrast, tumors that carried exon 9 mutations were more likely to be low-grade carcinomas. The Kaplan-Meier analysis suggested that p53 alterations (strong immunoexpression or mutations) conferred a worse prognosis (P ¼ 0.000). Although alterations in the PI3K-AKT signaling pathway alone did not influence overall survival, patients with deregulated PI3K-AKT pathway (PIK3CA and/or PTEN alterations) and p53 alterations had shorter survival (P ¼ 0.000) than patients with only p53 alterations. Such a relationship was lost when we considered exon 9 PIK3CA mutations. Our results contribute to further characterize the molecular genetic model for endometrial carcinogenesis.

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Endometrial carcinoma: pathology and genetics

Cited by 174 publications

References 150 publications

The Polymorphism of Hypoxia-inducible Factor-1a Gene in Endometrial Cancer

The Polymorphism of Hypoxia-inducible Factor-1a Gene in Endometrial Cancer

Wnt7a interaction with Fzd5 and detection of signaling activation using a split eGFP

Concomitant PI3K–AKT and p53 alterations in endometrial carcinomas are associated with poor prognosis

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