Molecular bases of endometrial cancer: New roles for new actors in the diagnosis and the therapy of the disease

Llauradó, Marta; Ruiz, Anna; Majem, Blanca; Ertekin, Tugçe; Colás, Eva; Pedrola, Núria; Devis, Laura; Rigau, Marina; Sequeiros, Tamara; Montes, Melania; García, Marta; Cabrera, Sílvia; Gil‐Moreno, Antonio; Xercavins, Jordi; Castellví, Josep; García, Ángel; Cajal, Santiago Ramón y; Moreno, Gema; Alameda, Francesc; Vazquez‐Levin, Mónica H.; Palacios, José; Prat, Jaime; Doll, Andreas; Matías‐Guiu, Xavier; Abal, Miguel; Reventós, Jaume

doi:10.1016/j.mce.2011.10.003

Cited by 58 publications

(50 citation statements)

References 99 publications

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“…2,24 We found loss of ARID1A in none of the hyperplasias without atypia and 16% of the complex hyperplasias with atypia, the latter considered to be the precursor of endometrioid endometrium carcinoma. Wiegand noted loss of ARID1A in atypical endometriosis adjacent to tumor, considered the precursor for ovarian endometrioid and clear-cell tumors, but not in a small set (9 cases) of complex atypical hyperplasia.…”

Section: Discussionmentioning

confidence: 74%

ARID1A loss is prevalent in endometrial hyperplasia with atypia and low-grade endometrioid carcinomas

et al. 2013

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ARID1A (AT-rich interactive domain 1A) has recently been identified as a tumor suppressor gene in various, predominantly gynecological cancers. We wanted to investigate the distribution of ARID1A in endometrial hyperplasia, carcinomas and metastatic lesions to elucidate the timing of expression loss of its protein ARID1A in the course of endometrial cancer carcinogenesis. In addition, we wanted to assess the relationship between the loss of ARID1A and clinicopathological variables in endometrial cancer in general and the endometrioid subtype in particular. We analyzed a prospectively collected series of 535 primary endometrial cancers, 77 metastatic lesions, as well as 38 retrospectively collected endometrial hyperplasias with evaluable immunohistochemical staining for ARID1A. Fresh frozen tissue was available for mRNA microarray analysis in 122 primary tumors in parallel. Loss of ARID1A protein expression was noted in none of the hyperplasias without atypia, 16% of hyperplasias with atypia, 19% of primary endometrioid tumors and 28% of metastatic lesions. Loss of ARID1A in primary tumor was significantly associated with endometrioid grade 1 or 2 and clearcell histology, diploid tumor cells, younger patient age and deeper myometrial infiltration, but not survival. ARID1A RNA expression was significantly correlated with ARID1A protein loss. Thus, loss of ARID1A appears to be an early event in the carcinogenesis of endometrioid uterine carcinomas and the association with deep myometrial infiltration may suggest an importance for invasiveness.

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Section: Discussionmentioning

confidence: 74%

ARID1A loss is prevalent in endometrial hyperplasia with atypia and low-grade endometrioid carcinomas

et al. 2013

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“…Usually, estrogen receptor (ER) and progesterone receptor (PR) expression are low or absent [14]. These types of tumors have P53 mutations, STK15 and HER2/neu over-expression, P16 over-expression and downregulation or loss of E-cadherin, and loss of heterozygosity (LOH) [15]. P53 expression is diffuse and proliferation index, which can be evaluated by KI-67, usually enhanced [16].…”

Section: Endometrial Cancer Classificationmentioning

confidence: 99%

“…The molecular alterations described in endometrioid carcinomas are: microsatellite instability (MSI), mutations in PTEN, K-RAS, PIK3CA, and b-catenin genes [15]. These types of alterations seem to be enrolled in malignant transformation, are detected on pre-malignant lesions, and are responsible for tumor progression.…”

Section: Molecular Profilementioning

confidence: 99%

Clinical translation for endometrial cancer stem cells hypothesis

Carvalho

Laranjo

Abrantes

et al. 2015

Cancer Metastasis Rev

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Endometrial cancer is the most frequent gynecological malignancy in developed world. Cancer stem cells (CSC) are recognized as a small proportion of cells among the tumor cell population that are capable of self-renewal, aberrant differentiation, and escape homeostasis. This review aims to systematize the existing evidence of CSC of endometrial cancer and its clinical translation. In endometrial cancer, the cancer stem cell hypothesis has been studied in vitro using the isolation of colony forming units, side population with dye efflux capacity, and tumorospheres. The stem cell markers for endometrial cancer do not have uniform characteristics, albeit CD133 and aldehyde dehydrogenase (ALDH) were being associated with CSC phenotype. The application of endometrial CSC on xenograft models proves the tumorigenic capacity of this small group of cells. The metastatic process has been explained due to epithelial-mesenchymal transition (EMT) in which CSC seems to have a critical role. The chemoresistance is characteristic of CSC that in endometrial cancer has been shown in CSC phenotype and associated with CSC markers. The most ambitious potential for CSC is the development of targeted therapies. Its application on endometrial cancer is still poor, being a future perspective for research.

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“…The majority of patients with sporadic endometrial cancers (approximately 80%) comprise of type I or estrogen-dependent endometrioid endometrial adenocarcinomas (Llauradó et al 2012). Prolonged exposure to estrogen promotes the development of endometrial hyperplasia, which may be without and with atypia.…”

Section: Introductionmentioning

confidence: 99%

DNA methylation as mechanism of apoptotic resistance development in endometrial cancer patients

Fialková

Vidomanová²,

Balhárek³

et al. 2017

gpb

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Abstract. DNA methylation is a significant epigenetic modification which plays a key role in regulation of gene expression and influences functional changes in endometrial tissue. Aberrant DNA methylation changes result in deregulation of important apoptotic proteins during endometrial carcinogenesis and apoptosis resistance development. Evading apoptosis is still a major problem in the successful treatment of endometrial cancer patients. The aim of our study was to examine the promoter DNA methylation changes in 22 apoptosis-associated genes in endometrioid endometrial cancer patients, precancerous lesions and healthy tissue from various normal menstrual cycle phases using a unique pre-designed methylation platform. We observed as the first a significant difference in promoter DNA methylation status in genes: BCL2L11 (p < 0.001), CIDEB (p < 0.03) and GADD45A (p < 0.05) during endometrial carcinogenesis and BIK gene (p < 0.03) in different phases of normal menstrual cycle. The results of our study indicate that deregulation of mitochondrial apoptotic pathway can considerably contributes to the apoptosis resistance development and may be helpful in identifying of new potent biomarkers in endometrial cancer.

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Molecular bases of endometrial cancer: New roles for new actors in the diagnosis and the therapy of the disease

Cited by 58 publications

References 99 publications

ARID1A loss is prevalent in endometrial hyperplasia with atypia and low-grade endometrioid carcinomas

ARID1A loss is prevalent in endometrial hyperplasia with atypia and low-grade endometrioid carcinomas

Clinical translation for endometrial cancer stem cells hypothesis

DNA methylation as mechanism of apoptotic resistance development in endometrial cancer patients

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