scholarly journals Loss of ten-eleven translocation 1 (TET1) expression as a diagnostic and prognostic biomarker of endometrial carcinoma

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259330
Author(s):  
Nien-Tzu Liu ◽  
Cherng-Lih Perng ◽  
Yu-Ching Chou ◽  
Pi-Shao Ko ◽  
Yi-Jia Lin ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Endometrial Carcinoma ◽  
Endometrial Hyperplasia ◽  
Expression Profiles ◽  
Gynecological Cancer ◽  
Dna Demethylation ◽  
Atypical Hyperplasia ◽  
Mrna Levels ◽  
Normal Endometrium ◽  
Expression Score

Endometrial carcinoma (EC) is the most common gynecological cancer. However, there is currently no routinely used biomarker for differential diagnosis of malignant and premalignant endometrial lesions. Ten-eleven translocation (TET) proteins, especially TET1, were found to play a significant role in DNA demethylation, via conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC). TET1, 5-mC, and 5-hmC expression profiles in endometrial carcinogenesis are currently unclear. We conducted a hospital-based retrospective review of the immunohistochemical expression of TET1, 5-mC, and 5-hmC in 181 endometrial samples. A “high” TET1 and 5-hmC expression score was observed in all cases of normal endometrium (100.0% and 100.0%, respectively) and in most samples of endometrial hyperplasia without atypia (90.9% and 78.8%, respectively) and atypical hyperplasia (90.6% and 93.8%, respectively), but a “high” score was found in only less than half of the EC samples (48.8% and 46.5%, respectively). The TET1 and 5-hmC expression scores were significantly higher in normal endometrium and premalignant endometrial lesions than in ECs (p < 0.001). A “high” 5-mC expression score was observed more frequently for ECs (81.4%) than for normal endometrium (40.0%), endometrial hyperplasia without atypia (51.5%), and atypical hyperplasia (53.1%) (p < 0.001). We also found that TET1 mRNA expression was lower in ECs compared to normal tissues (p = 0.0037). TET1 immunohistochemistry (IHC) scores were highly proportional to the TET1 mRNA levels and we summarize that the TET1 IHC scoring can be used for biomarker determinations. Most importantly, a higher TET1 score in EC cases was associated with a good overall survival (OS) rate, with a hazard ratio (HR) of 0.31 for death (95% confidence interval: 0.11–0.84). Our findings suggest that TET1, 5-mC, and 5-hmC expression is a potential histopathology biomarker for the differential diagnosis of malignant and premalignant endometrial lesions. TET1 is also a potential prognostic marker for EC.

Aberrant Expression of the Von Hippel-Lindau Gene in Human Endometrial Hyperplasia and Endometrial Carcinoma

2011 ◽  
Vol 21 (3) ◽  
pp. 430-434 ◽  
Author(s):  
Jian-Ying Xu ◽  
Wei-Jie Zhu ◽  
Xiao-Zhe Cao ◽  
Xian-Feng Li ◽  
Jin Wu
Keyword(s):  
Endometrial Carcinoma ◽  
Western Blotting ◽  
Endometrial Hyperplasia ◽  
Atypical Hyperplasia ◽  
Mrna Levels ◽  
Simple Complex ◽  
Normal Endometrium ◽  
Aberrant Expression ◽  
Vhl Gene ◽  
Von Hippel Lindau

IntroductionThe purpose of this study was to determine whether aberrant expression of the von Hippel-Lindau (VHL) gene in human hyperplastic and malignant endometrial tissues was involved in endometrial carcinogenesis.MethodsFresh tissue samples of endometrial hyperplasia consisting of simple (n = 26), complex (n = 23), and atypical hyperplasia (n = 20); endometrial carcinoma (n = 17); and normal endometrium (n = 40) were measured using Western blotting and real-time reverse transcription polymerase chain reaction. Paraffin-embedded sections of endometrial hyperplasia (n = 90), endometrial carcinoma (n = 30), and normal endometrium (n = 60) were detected by immunohistochemical method.ResultsVon Hippel-Lindau staining was present in the cytoplasm of epithelial cells and stroma. A decreased expression of VHL mRNA in endometrial hyperplasia from simple, complex, to atypical hyperplasia was observed. There were statistical differences on VHL messenger RNA (mRNA) levels among simple, complex, and atypical hyperplasia (P < 0.01). The VHL mRNA levels in endometrial carcinoma were significantly lower than those in normal endometrium, simple hyperplasia, or complex hyperplasia (P < 0.01) but similar to those in atypical hyperplasia (P > 0.05). Von Hippel-Lindau protein levels by Western blotting and staining intensity by immunohistochemistry were coincident with the VHL mRNA levels.ConclusionsAberrant expression of the VHL gene is associated with the risk of endometrial hyperplasia progressing to endometrial carcinoma, and its expression levels are useful as a predictive indicator for endometrial carcinoma.

scholarly journals Differential diagnosis between normal endometrium and endometrial hyperplasia with immunostaining cytology using anti-LeY monoclonal antibody

2003 ◽  
Vol 13 (1) ◽  
pp. 42-46
Author(s):  
Y. Arai ◽  
M. Nishida
Keyword(s):  
Monoclonal Antibody ◽  
Differential Diagnosis ◽  
Endometrial Cancer ◽  
Endometrial Carcinoma ◽  
Endometrial Hyperplasia ◽  
Negative Staining ◽  
Positive Staining ◽  
Normal Endometrium ◽  
Number Of Cells

We have previously reported that both endometrial cancer and endometrial hyperplasia stain positively for the anti-LeY monoclonal antibody, whereas normal endometrium does not. Endometrial hyperplasia is a premalignant change associated with the eventual development of endometrial carcinoma. However, it can be difficult to differentiate hyperplasia from normal endometrium in cytology. This study illustrates the use of immunocytochemical cytology using anti-LeY monoclonal antibody to differentiate between endometrial hyperplasia and normal endometrium. Immunostaining using anti-LeY monoclonal antibody was performed on cytologic specimens obtained from 17 normal endometria, 25 endometria with endometrial hyperplasia, and 13 endometria with endometrial carcinoma. All normal endometria displayed negative staining for anti-LeY monoclonal antibody, whereas all endometria with endometrial carcinoma displayed positive staining. Of the endometrial hyperplasia cases, 21 displayed positive staining. However, four displayed negative staining due to the small number of cells available for diagnosis. We believe that immunostaining cytology using anti-LeY monoclonal antibody is a useful method for differentiating between normal endometrium and endometrial hyperplasia.

scholarly journals Pyruvate Kinase M2 Expression: A Potential Metabolic Biomarker to Differentiate Endometrial Precancer and Cancer That Is Associated with Poor Outcomes in Endometrial Carcinoma

2019 ◽  
Vol 16 (23) ◽  
pp. 4589
Author(s):  
Lai ◽  
Chou ◽  
Lin ◽  
Yu ◽  
Ou ◽  
...  
Keyword(s):  
Endometrial Carcinoma ◽  
Pyruvate Kinase ◽  
Poor Prognosis ◽  
Endometrial Hyperplasia ◽  
Atypical Hyperplasia ◽  
Poor Overall Survival ◽  
Normal Endometrium ◽  
Cytoplasmic Staining ◽  
Pyruvate Kinase M2 ◽  
Poor Outcomes

Background: Pyruvate kinase M2 (PKM2) is a regulator of the processes of glycolysis and oxidative phosphorylation, but the roles that it plays in endometrial cancer remain largely unknown. This study evaluated the PKM2 expression in normal endometrium, endometrial hyperplasia, and endometrial carcinoma, and its prognostic value was investigated in endometrial carcinoma patients. Methods: A hospital-based retrospective review was conducted to examine the immunohistochemical PKM2 distribution in 206 endometrium samples from biopsies or hysterectomies. The immunoreactivity of PKM2 was divided into groups of low and high scores according to the extent and intensity of staining. Results: Intense cytoplasmic staining was observed for the PKM2 protein in malignant endometrial lesions. A high PKM2 score was observed in many endometrial carcinoma samples (50.0%), but there was a low percentage in endometrial atypical hyperplasia (12.5%). High PKM2 expression was not found in the normal endometrium (0.0%) nor endometrial hyperplasia without atypia (0.0%). The PKM2 protein score was significantly higher in endometrial carcinoma samples than premalignant endometrial lesions (p < 0.001). Notably, higher PKM2 scores in cases of endometrial carcinoma correlated with poor overall survival (p = 0.006), and the hazard ratio for death was 3.40 (95% confidence interval, 1.35–8.56). Conclusions: Our results indicate that the prevalence of PKM2high tumor cells in endometrial carcinoma is significantly associated with worse prognostic factors and favors a poor prognosis. The expression of PKM2 is also a potential histopathological biomarker for use in the differential diagnosis of malignant and premalignant endometrial lesions.

Human telomerase RNA as endogenous control in endometrial tissue

2005 ◽  
Vol 15 (2) ◽  
pp. 343-348
Author(s):  
M. Paul-Samojedny ◽  
A. Witek ◽  
A. Samojedny ◽  
A. Witkowska ◽  
T. Wilczok
Keyword(s):  
Reverse Transcriptase ◽  
Endometrial Hyperplasia ◽  
Expression Profiles ◽  
Quantitative Polymerase Chain Reaction ◽  
Endometrial Adenocarcinoma ◽  
Endometrial Tissue ◽  
Endogenous Control ◽  
Telomerase Rna ◽  
Normal Endometrium ◽  
Human Telomerase

Telomerase is a reverse transcriptase that adds repetitive telomere sequences to the end of chromosomes, which is thought to be essential for cellular immortality and oncogenesis. The enzyme consists of three subunits: human telomerase reverse transcriptase (hTERT), human telomerase RNA (hTR), and telomerase protein 1 (TP1). The hTERT subunit determines the activity of telomerase as an enzyme and is detected in most human tumors and regenerative cells. But many studies have revealed that hTR and TP1 are expressed constitutively. This resuts suggest that the hTR and TP1 subunits may be potentially good markers of endogenous RNA control. Endometrial dating was determined from the pathomorphology of the endometrium and classified into normal proliferative endometrium, endometrial hyperplasia (simple, complex, and atypical), and endometrial adenocarcinoma. The analysis of the expression of the hTERT, TP1, and hTR telomerase subunits was performed by a quantitative polymerase chain reaction method, based on fluorescent TaqMan methodology (ABI Prism 7 700 Sequence Detection System) capable of measuring fluorescence in real time. The aim of the study was an analysis of the expression profiles of genes encoding hTR and TP1 telomerase subunits in normal endometrium, endometrial hyperplasia, and adenocarcinoma forthe estimation of the possibility of once application in endogenous RNA control of gene analysis in the endometrium. The nonparametric Mann–Whitney U test and analysis of variance Friedman test were used to evaluate the variation in telomerase subunit mRNA level between normal endometrium, and endometrial hyperplasia and adenocarcinoma. The results confirm the hTR subunit expression as a good marker of endogenous control in quantitative analysis of gene transcription in endometrial tissue. TP1 subunit transcriptions have not been detected constitutively in our study.

scholarly journals Preoperative and postoperative histopathological findings in patients with endometrial hyperplasia

2007 ◽  
Vol 60 (7-8) ◽  
pp. 372-376 ◽  
Author(s):  
Biljana Djordjevic ◽  
Zorica Stanojevic ◽  
Vesna Zivkovic ◽  
Dusan Lalosevic ◽  
Jasmina Gligorijevic ◽  
...  
Keyword(s):  
Endometrial Carcinoma ◽  
Endometrial Hyperplasia ◽  
Atypical Hyperplasia ◽  
Histopathological Diagnosis ◽  
Cytological Atypia ◽  
Histopathological Findings ◽  
Female Patients

Introduction. The aim of this study was to analyze and compare the histopathological findings in curettage and hysterectomy specimens, to evaluate the accuracy of histopathological diagnosis in curettage specimens, and to determine the frequency of coexisting endometrial carcinoma in patients with histopathological diagnosis of endometrial hyperplasia. Material and methods. Curettage and hysterectomy specimens of 135 female patients with initially diagnosed endometrial hyperplasia were retrospectively analyzed and compared. Results. Simple hyperplasia was found in 49 patients (36.3%), complex hyperplasia in 14 (10.4%), simple atypical hyperplasia in 24 (17.8%), and complex atypical hyperplasia in 48 (35.5%) patients. After hysterectomy, 59 (43.7%) patients were found to have simple hyperplasia, 12 (8.9%) complex hyperplasia, 15 (11.1%) simple atypical hyperplasia, 18 (20.7%) complex atypical hyperplasia, and 21 (15.5%) endometrial carcinoma. The accuracy of histopathological diagnosis of endometrial hyperplasia in curettage specimens was 82.2-89.6% and dependent on the types of hyperplasia. The frequency of coexisting endometrial carcinoma was significantly higher (p<0.001) in patients with atypical hyperplasia than in patients with hyperplasia without cytological atypia. After hysterectomy, coexisting endometrial carcinoma was found in 27.8% of patients with histopathological diagnosis of atypical hyperplasia in curettage specimens. In contrast to simple atypical hyperplasia, the frequency of coexisting endometrial carcinoma was significantly higher (p<0.05) in complex atypical hyperplasia. Conclusion. The frequency of coexisting endometrial carcinoma in hysterectomy specimens in patients with histopathological diagnosis of atypical hyperplasia in curettage specimens was relatively high and it should be taken into account when planning therapy. .

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