scholarly journals PTENSequence Analysis in Endometrial Hyperplasia and Endometrial Carcinoma in Slovak Women

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
H. Gbelcová ◽  
P. Bakeš ◽  
P. Priščáková ◽  
V. Šišovský ◽  
I. Hojsíková ◽  
...  

Phosphatase and tensin homolog (PTEN) is a protein that acts as a tumor suppressor by dephosphorylating the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. Loss of PTEN function has been implicated in the pathogenesis of a number of different tumors, particularly endometrial carcinoma (ECa). ECa is the most common neoplasia of the female genital tract. Our study evaluates an association between the morphological appearance of endometrial hyperplasia and endometrial carcinoma and the degree ofPTENalterations. A total of 45 endometrial biopsies from Slovak women were included in present study. Formalin-fixed and paraffin-embedded tissue samples with simple hyperplasia (3), complex hyperplasia (5), atypical complex hyperplasia (7), endometrioid carcinomas G1 (20) and G3 (5), and serous carcinoma (5) were evaluated for the presence of mutations in coding regions ofPTENgene, the most frequently mutated tumor suppressor gene in endometrial carcinoma. 75% of the detected mutations were clustered in exons 5 and 8. Out of the 39 mutations detected in 24 cases, 20 were frameshifts and 19 were nonsense, missense, or silent mutations. Some specimens harboured more than one mutation. The results of current study on Slovak women were compared to a previous study performed on Polish population. The two sets of results were similar.

Author(s):  
Alpana Laisom ◽  
Gayatri Pukhrambam ◽  
Yumnam Shameen ◽  
Ningthibi Akoijam ◽  
Prasanta Sinam ◽  
...  

Abstract Introduction: Endometrial carcinoma (EC) is the most common gynaecological malignancy in developed countries and has been classified into two groups, type 1 and type 2.  Type 1 or endometrioid endometrial carcinomas (EECA) accounts for 80% of EC and are thought to develop following a continuum of premalignant lesions ranging from endometrial hyperplasia without atypia (EH) and atypical hyperplasia (AH). PTEN (phosphatase and tensin homolog), a tumor suppressor gene is commonly inactivated in 83 % of endometrioid carcinoma and 55% of precancerous lesions. Cyclin D1, a cell cycle regulator is overexpressed in about 40% of endometrial carcinomas. Aim: To study the expression of PTEN (Phosphatase and tensin homolog) and Cyclin D1 in non-neoplastic and neoplastic endometrial lesions by immunohistochemistry (IHC). Methods: A 2 year cross-sectional study (September 2017 to August 2019) on 115 endometrial samples was done in the Department of Pathology, RIMS. Histomorphological features and IHC expression of PTEN and Cyclin D1 in the various endometrial lesions were studied and evaluated, data collected in IBM SPSS Statistics 21 was statistically analyzed using Chi - square  and Fisher’s Exact test. Results: Out of the 115 cases, 47(40.9%) were diagnosed as benign proliferative endometrium, 20(17.4%) benign secretory endometrium, 21(18.3%) hyperplasia without atypia, 15(13.0%)  atypical hyperplasia and 12(10.4%) endometrial carcinoma with an age group spanning from 26-68 years (mean age = 46.4).  Following IHC staining, 91.7%(11/12) and 83.3%(10/12) cases of EC and 80%(12/15) and 73.3%(11/15) cases of AH showed complete loss of PTEN expression and Cyclin D1 overexpression, respectively when compared to other benign lesions and was statistically significant  (p < .001). Conclusion: Loss of PTEN and Cyclin D1 overexpression was seen in a significant number of EECA and AH, suggesting both as an early event in endometrial carcinogenesis. Therefore, we propose the use of PTEN and Cyclin D1 immunostaining as an adjunct to histopathological diagnosis as it may be informative in the identification and further management of  premalignant endometrial  lesions that are likely to progress to carcinoma Keywords: PTEN, Cyclin D1, endometrial hyperplasia, endometrial carcinoma, endometrioid endometrial carcinomas.


Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 435 ◽  
Author(s):  
Chiara Bazzichetto ◽  
Fabiana Conciatori ◽  
Matteo Pallocca ◽  
Italia Falcone ◽  
Maurizio Fanciulli ◽  
...  

Identifying putative biomarkers of clinical outcomes in cancer is crucial for successful enrichment, and for the selection of patients who are the most likely to benefit from a specific therapeutic approach. Indeed, current research in personalized cancer therapy focuses on the possibility of identifying biomarkers that predict prognosis, sensitivity or resistance to therapies. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor gene that regulates several crucial cell functions such as proliferation, survival, genomic stability and cell motility through both enzymatic and non-enzymatic activities and phosphatidylinositol 3-kinase (PI3K)-dependent and -independent mechanisms. Despite its undisputed role as a tumor suppressor, assessment of PTEN status in sporadic human tumors has yet to provide clinically robust prognostic, predictive or therapeutic information. This is possibly due to the exceptionally complex regulation of PTEN function, which involves genetic, transcriptional, post-transcriptional and post-translational events. This review shows a brief summary of the regulation and function of PTEN and discusses its controversial aspects as a prognostic/predictive biomarker.


2018 ◽  
Vol 13 (1) ◽  
pp. 155798831881690 ◽  
Author(s):  
Binshuai Wang ◽  
Mingyuan Liu ◽  
Yimeng Song ◽  
Changying Li ◽  
Shudong Zhang ◽  
...  

KLF2, a member of the Kruppel-like factor (KLF) family, is thought to be a tumor suppressor in many kinds of malignant tumors. Its functions in prostate cancer (PCa) are unknown. This study aimed to explore the role of KLF2 in the migration and invasion of PCa cells. The expression of KLF2 was measured by immunohistochemistry in PCa tissues and in paired non-tumor tissues. KLF2 and MMP2 expression in cells was measured by Western blot and RT-qPCR. Adenoviruses and siRNAs were used in cell function tests to investigate the role of KLF2 in regulating MMP2. Interactions between KLF2 and MMP2 were analyzed by a luciferase activity assay. The present study, for the first time, identified that KLF2 was downregulated both in PCa clinical tissue samples and in cancer cell lines. The overexpression of KLF2 inhibited the migration and invasion of PCa cells via the suppression of MMP2.This study demonstrates that KLF2 might act as a tumor suppressor gene in PCa and that the pharmaceutical upregulation of KLF2 may be a potential approach for treatment.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Magdy M Abd Elgawaad ◽  
Amr M El Helaly ◽  
Malames M Faisal ◽  
Asmaa F Kasem

Abstract Background Endometrial carcinoma is the most common gynecological malignancy in the developed countries and the third common gynecological malignancy in Egypt after breast and ovarian cancers. Aim of the Work to evaluate this risk scoring model on Egyptian patients and to study the effect of adding other patient characteristics (DM, BMI and relevant family history) on the sensitivity and specificity of RHEA scoring model. Patients and Methods The current study was conducted in Ain Shams University Maternity Hospital in the period between September 2017 and December 2018. A total of 100 women with postmenopausal bleeding and endometrial thickness &gt; 4mm were included in the study. Results Histological examination revealed that benign pathology (n = 65) (73%) was found to be: most common cause was endometrial hyperplasia without atypia (20.3%) followed by chronic endometritis (13.5%), then endometrial polyp (11.3%), cystic atrophy of endometrium (8.9%), proliferative endometrium (8.9%), endometrial hyperplasia with atypia (6.7%) and lastly mucous polyp (3.4%) while malignant histopathology(n = 24)(27%) which is significantly higher than the international rates showed: Endometriod adenocarcinoma (n = 19)(21.3%), papillary serous carcinoma (n = 4)(4.5%) and undifferentiated carcinoma (n = 1)(1.1%). The current study showed that RHEA score performs in our study population with a comparable validity to that reported by its inventors with sensitivity 79.2% (57.8% - 92.9%) vs. 87.5% and specificity 84.6% (73.5% - 92.4%) vs. 80.1% respectively. In results of the current study it was found that the time since onset of menopause rather than age was associated with endometrial cancer with the optimum cut-off for postmenopausal duration was estimated to be 9 years achieving a sensitivity of 87.5% and a specificity of 60.0%, but it needs multivariate analysis on larger and more representative sample size to confirm this association, A statistically significant regression model was including only postmenopausal duration, recurrent bleeding and endometrial thickness. None of age, BMI, family history or hypertension proved a statistically significant predictive effect after adjustment for other predictive variables. Conclusion Taking in consideration the higher prevalence of endometrial carcinoma in the sample of the current study, the wide 95% confidence intervals for the different validity indices for the RHEA scores derived from this study, it seems that RHEA score performs in this study population with a comparable validity to that reported by its inventors.


Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1169 ◽  
Author(s):  
Sioletic Stefano ◽  
Scambia Giovanni

Soft tissue sarcoma (STS) is a rare malignancy of mesenchymal origin classified into more than 50 different subtypes with distinct clinical and pathologic features. Despite the poor prognosis in the majority of patients, only modest improvements in treatment strategies have been achieved, largely due to the rarity and heterogeneity of these tumors. Therefore, the discovery of new prognostic and predictive biomarkers, together with new therapeutic targets, is of enormous interest. Phosphatase and tensin homolog (PTEN) is a well-known tumor suppressor that commonly loses its function via mutation, deletion, transcriptional silencing, or protein instability, and is frequently downregulated in distinct sarcoma subtypes. The loss of PTEN function has consequent alterations in important pathways implicated in cell proliferation, survival, migration, and genomic stability. PTEN can also interact with other tumor suppressors and oncogenic signaling pathways that have important implications for the pathogenesis in certain STSs. The aim of the present review is to summarize the biological significance of PTEN in STS and its potential role in the development of new therapeutic strategies.


Cancer ◽  
2008 ◽  
Vol 114 (3) ◽  
pp. 155-164 ◽  
Author(s):  
Yoshiaki Norimatsu ◽  
Motoyuki Miyamoto ◽  
Tadao K. Kobayashi ◽  
Takuya Moriya ◽  
Keiko Shimizu ◽  
...  

1997 ◽  
Vol 66 (3) ◽  
pp. 449-453 ◽  
Author(s):  
Fu-Shing Liu ◽  
Esther Shih-Chu Ho ◽  
Rocky Tai-Ping Shih ◽  
Ai Shih

2021 ◽  
Vol 12 ◽  
Author(s):  
Tianyu He ◽  
Xiaoyun Zhang ◽  
Jianyu Hao ◽  
Shigang Ding

The Phosphatase and tensin homolog (PTEN) gene is one of the most important tumor suppressor genes, which acts through its unique protein phosphatase and lipid phosphatase activity. PTEN protein is widely distributed and exhibits complex biological functions and regulatory modes. It is involved in the regulation of cell morphology, proliferation, differentiation, adhesion, and migration through a variety of signaling pathways. The role of PTEN in malignant tumors of the digestive system is well documented. Recent studies have indicated that PTEN may be closely related to many other benign processes in digestive organs. Emerging evidence suggests that PTEN is a potential therapeutic target in the context of several non-neoplastic diseases of the digestive tract. The recent discovery of PTEN isoforms is expected to help unravel more biological effects of PTEN in non-neoplastic digestive diseases.


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