Prognostic Value of E-Cadherin Expression and CDH1 Promoter Methylation in Patients With Endometrial Carcinoma

Yi, Tie-Zhong; Guo, Jing; Zhou, Lili; Chen, Xing; Ruoran, MI; Qu, Quanxin; Zheng, Jie; Zhai, Ling

doi:10.3109/07357907.2010.512603

Cited by 29 publications

(24 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A few studies have evaluated the promoter methylation of CDH1/E-cadherin, a possible tumor-suppressor gene, in endometrial cancer (14,(46)(47)(48)(49). In the present study, we detected CpG promoter methylation of this gene in 31.4% of EEC samples, 21.1% of EHP cases and in 20.0% of cases with healthy endometrium.…”

Section: Rassf1a Gstp1 Cdh1supporting

confidence: 56%

“…A higher methylation rate of the CDH1 gene (42.9% in EEC) was detected by Kang et al (36) who also described the high frequency of this event in cervical squamous cell carcinoma (80.6%). The association between CDH1 promoter hypermethylation and endometrial cancer was also analyzed by Yi et al (49) who found that the hypermethylation of the CDH1 promoter, which caused low expression of E-cadherin in endometrial cancer, was associated with not only clinicopathological progression of endometrial cancer but also with the overall 5-year clinical survival rate. The findings provide a potential therapeutic and prognostic target molecule for patients with endometrial cancer.…”

Section: Rassf1a Gstp1 Cdh1mentioning

confidence: 95%

See 1 more Smart Citation

Promoter hypermethylation of the tumor-suppressor genes RASSF1A, GSTP1 and CDH1 in endometrial cancer

et al. 2013

View full text Add to dashboard Cite

Abstract. Endometrial cancer is a common gynecological malignancy with a good prognosis in early stages of the disease. The CpG island in the promoter region of tumorsuppressor genes are frequently methylated in various types of human cancers. In the present study, we examined the methylation status of the GSTP1, CDH1 and RASSF1A genes in endometrioid endometrial cancer (EEC), endometrial complex hyperplasia (EHP) and healthy endometrium with the aim to identify correlations between promoter hypermethylation, disease risk and clinicopathological parameters. A nested two-stage methylation-specific PCR (MSP) was performed to analyze the promoter CpG methylation status of GSTP1, CDH1 and RASSF1A genes in the population studied. A total of 92 subjects were initially included in the study of which 41 EEC, 19 EHP and 20 controls were processed for final analyses. A significant difference was found between the study groups and the presence of promoter CpG hypermethylation status in the GSTP1 (P<0.05) and RASSF1A (P<0.0001) genes. RASSF1A, GSTP1 and CDH1 gene promoter methylation was present in 85.4, 68.3 and 31.4% of EEC samples when compared to that in the controls with 30.0, 35.0 and 20.0%, respectively. CpG methylation of all three investigated tumor-suppressor genes was found in 12.2% of EEC patients, in 4.2% of EHP patients and in 3.7% of the controls, respectively. Positive findings for the promoter methylation of two investigated genes were found in 48.7% of EEC patients, 26.0% of EHP patients and in 18.5% of the controls. With regard to histopathological variables and CpG methylation, we found significant correlations between the RASSF1A and GSTP1 genes and higher tumor grade, deeper myometrial invasion and positive metastatic involvement of pelvic lymph nodes. No associations were noted between promoter hypermethylation of the CDH1 gene and biological features of the endometrial cancer cases. The results indicate that aberrant CpG methylation of the promoter region in the GSTP1 and RASSF1A tumor-suppressor genes is an important event in carcinogenesis of endometrial cancer and may have an impact on tumor aggressiveness. Finally, the present study suggests that epigenetic alterations may be of diagnostic value for the better clinical management of premalignant endometrial lesions.

show abstract

Section: Rassf1a Gstp1 Cdh1supporting

confidence: 56%

Section: Rassf1a Gstp1 Cdh1mentioning

confidence: 95%

Promoter hypermethylation of the tumor-suppressor genes RASSF1A, GSTP1 and CDH1 in endometrial cancer

et al. 2013

View full text Add to dashboard Cite

show abstract

“…As previously shown, CDH1 expression is often reduced or completely inactivated by promoter methylation. A low E-cadherin expression is associated with worse prognosis, higher stage and greater metastatic potential (39). Our previous experiments conducted on breast and colon cancer lines confirm that an increase of WWOX expression level results in changes in cell behavior (23, unpublished data).…”

Section: Discussionmentioning

confidence: 61%

The WWOX tumor suppressor gene in endometrial adenocarcinoma

Płuciennik

Kośla

Wójcik‐Krowiranda

et al. 2013

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Abstract. Endometrial cancer is a lethal malignancy, the causes of which remain to be determined. The aim of the present study, carried out on tumor samples from 79 patients, was to evaluate the role of the WWOX tumor suppressor gene in endometrial adenocarcinoma. The expression levels of WWOX and its protein content were assessed in normal endometrium and cancer samples. Quantitative PCR was used to assess the correlation between the expression levels of WWOX and the genes involved in the proliferation (MKI67), apoptosis (BAX, BCL2), signal transduction (EGFR), cell cycle (CCNE1, CCND1), cell adhesion (CDH1) and transcription regulation (TP73, NCOR1). The relationship between loss of hetero zygosity (LOH) and WWOX mRNA levels was also investigated using high resolution melting. Results of the present study demonstrated a positive correlation of WWOX expression with BCL2 and CCND1 and a negative correlation with BAX, CDH1, NCOR1 and BCL2/BAX ratio. The results also showed that loss of heterozygosity at two analyzed loci of the WWOX gene is frequent in patients with endometrial cancer and that WWOX expression levels are lower in tumor samples than in normal tissue. In conclusion, WWOX may be involved in endometrial cancer.

show abstract

“…[17]. The loss of E-cadherin expression in EEC is associated not only with the CDH1 gene mutations [17], but also with CDH1 promoter hypermethylation [18] and dysregulation of the proteins, which normally inhibit the E-cadherin expression. The loss of E-cadherin expression is a poor prognostic factor for the patients with EEC [10], because this loss is associated with the phenomenon of epithelial-mesenchymal transformation, which includes the loss of apical-basal polarity of the cancer cells, the increasing of the mesenchymal integrins synthesis by these cells, the migration of the tumor cells into the adjacent tissues and also the tumor metastasis [19].…”

Section: Resultsmentioning

confidence: 99%

Comparative characteristics of the transcriptional activity of CDH1, CTNNB1, VEGFA genes and expression of proteins E-cadherin, β-catenin and VEGFA, coded by these genes in metastatic and non-metastatic endometrioid endometrial carcinoma

2016

View full text Add to dashboard Cite

The violation of Wnt-signaling pathway and cyclic neoangiogenesis is early events in endometrial carcinogenesis. In this process an important role is played by epigenetic modifi cations and mutations of CDH1, CTNNB1, VEGFA genes, followed by expression violations of E-cadherin, β-catenin, VEGFA encoded by them.The aim. To study the expression levels of mRNA of CDH1, CTNNB1, VEGFA genes and the expression levels of E-cadherin, β-catenin, VEGFA in non-metastatic endometrioid endometrial carcinoma (EEC) and in EEC with metastases to regional lymph nodes. Materials and methods.Immunohistochemical study of invasive рТ 1-4 N 0 M x endometrioid endometrial carcinoma (EEC) (n=56; age -42-83 years), invasive рТ 1-4 N 1-2 M x EEC (n=30; age -48-79 years), samples of normal proliferative endometrium (PE) (n=30; age -41-62 years) was performed. Molecular-genetic study of invasive рТ 1-4 N 0 M x EEC (n=10; age -45-67 years), invasive рТ 1-4 N 1-2 M x EEC (n=10; age -44-63 years), samples of PE (n=10; age -46-59 years) was performed.Results. EEC is characterized by the lower mRNA expression level of CDH1 gene and by the higher mRNA expression levels of CTNNB1, VEGFA genes in comparison with the PE. E-cadherin expression level is 32.6 % lower in non-metastatic EEC and also is 58.10 % lower in metastatic EEC in comparison with the PE. β-catenin expression level is 32.56 % lower in non-metastatic EEC and also is 58.11 % lower in metastatic EEC in comparison with the PE. VEGFA expression level is 27.72 % higher in non-metastatic EEC and also is 17.87 % higher in metastatic EEC in comparison with the PE. There is lower β-catenin expression level in metastatic EEC in comparison with non-metastatic EEC. Non-metastatic and metastatic EEC is characterized by the direct medium connections between the mRNA expression levels of CTNNB1 and VEGFA genes (γ=0.44), between the mRNA expression level of CTNNB1 gene and VEGFA expression level in the tumor (γ=0.37).Conclusions. These changes contribute to tumor growth, invasion and metastasis.Порівняльна характеристика транскрипційної активності генів CDH1, CTNNB1, VEGFA та експресії кодованих ними білків Е-кадгерину, β-катеніну та VEGFA в метастатичній ендометріоїдній аденокарциномі тіла матки і в аденокарциномі без метастазів В. О. Туманський, О. В. Чепець, О. М. КамишнийУ канцерогенезі рака ендометрію ранніми подіями є порушення Wnt-сигнального шляху та циклічного ангіогенезу. Важли-ву роль при цьому відіграють епігенетичні модифікації генів і мутації генів CDH1, CTNNB1, VEGFА з дальшим порушенням експресії кодованих ними протеїнів -Е-кадгерину, β-катеніну, VEGFА.Мета роботи -вивчити молекулярно-генетичними методами рівень експресії мРНК генів CDH1, CTNNB1, VEGFА, імуно-гістохімічним методом -рівні експресіі Е-кадгерину, β-катеніну, VEGFA в ендометріоїдній аденокарциномі ендометрію без метастазів і з метастазами в регіонарні лімфовузли.Матеріали та методи. Імуногістохімічним методом вивчена інвазивна рТ 1-4 N 0 M х G 1-3 ендометріоїдна аденокарцинома ен-дометрію (ЕАЕ) (n=56; вік -42-83 роки), ...

show abstract

Prognostic Value of E-Cadherin Expression and CDH1 Promoter Methylation in Patients With Endometrial Carcinoma

Cited by 29 publications

References 29 publications

Promoter hypermethylation of the tumor-suppressor genes RASSF1A, GSTP1 and CDH1 in endometrial cancer

Promoter hypermethylation of the tumor-suppressor genes RASSF1A, GSTP1 and CDH1 in endometrial cancer

The WWOX tumor suppressor gene in endometrial adenocarcinoma

Comparative characteristics of the transcriptional activity of CDH1, CTNNB1, VEGFA genes and expression of proteins E-cadherin, β-catenin and VEGFA, coded by these genes in metastatic and non-metastatic endometrioid endometrial carcinoma

Contact Info

Product

Resources

About