Conservative Medroxyprogesterone Acetate Therapy in Early Stage of Endometrial Carcinoma Associated with Phosphatase and Tensin Homolog Expression

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.

Download Full-text

Unsuspected Uterine Carcinosarcoma (heterologous) Diagnosed following Conservative Therapies with Medroxyprogesterone Acetate for Presumed Early-Stage Endometrial Carcinoma

American Journal of Reproductive Immunology ◽

10.1034/j.1600-0897.2002.1c068.x ◽

2002 ◽

Vol 47 (3) ◽

pp. 129-131 ◽

Cited By ~ 5

Author(s):

HIROYUKI FUJIWARA ◽

HIROAKI SHIBAHARA ◽

RIE USUI ◽

SATORU TAKAMIZAWA ◽

SHUICHI KOSUGE ◽

...

Keyword(s):

Endometrial Carcinoma ◽

Medroxyprogesterone Acetate ◽

Early Stage ◽

Uterine Carcinosarcoma

Download Full-text

Significance of p27 as a predicting marker for medroxyprogesterone acetate therapy against endometrial endometrioid adenocarcinoma

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200602001-00086 ◽

2006 ◽

Vol 16 (Suppl 1) ◽

pp. 452-457 ◽

Cited By ~ 3

Author(s):

J. Watanabe ◽

K. Watanabe ◽

T. Jobo ◽

Y. Kamata ◽

M. Kawaguchi ◽

...

Keyword(s):

Endometrial Carcinoma ◽

Medroxyprogesterone Acetate ◽

Early Stage ◽

Endometrial Adenocarcinoma ◽

Endometrioid Adenocarcinoma ◽

Nuclear Staining ◽

Adenocarcinoma Cells ◽

Clinical Responses ◽

Effective Group ◽

Endometrial Endometrioid Adenocarcinoma

Watanabe J, Watanabe K, Jobo T, Kamata Y, Kawaguchi M, Imai M, Okayasu I, Kuramoto H. Significance of p27 as a predicting marker for medroxyprogesterone acetate therapy against endometrial endometrioid adenocarcinoma. Int J Gynecol Cancer 2006;16(Suppl. 1): 452–457.We reported that p27 induced by medroxyprogesterone acetate (MPA) may be involved in the progestin-induced growth suppression of human endometrial adenocarcinoma cells. This study aimed at investigating whether p27 expression could be a predicting marker to evaluate the effectiveness of MPA therapy. The clinical responses of 15 patients with endometrial carcinoma treated with MPA were examined. p27 expression was evaluated by immunohistochemical staining. Percentage of positive nuclear staining was expressed as a strongly positive (SP) labeling index (LI). Before MPA treatment, SP LIs in the effective and noneffective groups were 22.6 ± 14.3% and 9.1 ± 9.2%. At 1–6 weeks in the MPA treatment, SP LIs increased in both groups and were significantly higher than those before the therapy. At 7–12 weeks, SP LIs in both groups decreased to the level of pretherapy. At 13–18 weeks, SP LIs in the effective group were 14.9 ± 5.7%, whereas in the noneffective group, 1.1 ± 2.0%. The former was significantly higher than the latter. p27 expression could predict the effectiveness of MPA treatment for endometrial carcinoma at an early stage of the 4-month period in MPA therapy and could be a useful predicting marker for MPA.

Download Full-text

IMMUNOHISTOCHEMICAL STUDY ON PTEN AND CYCLIN D1 IN NON-NEOPLASTIC AND NEOPLASTIC ENDOMETRIAL LESIONS

International Journal of Medical and Biomedical Studies ◽

10.32553/ijmbs.v5i7.1969 ◽

2021 ◽

Vol 5 (7) ◽

Author(s):

Alpana Laisom ◽

Gayatri Pukhrambam ◽

Yumnam Shameen ◽

Ningthibi Akoijam ◽

Prasanta Sinam ◽

...

Keyword(s):

Cyclin D1 ◽

Endometrial Carcinoma ◽

Endometrial Hyperplasia ◽

Precancerous Lesions ◽

Atypical Hyperplasia ◽

Histopathological Diagnosis ◽

Phosphatase And Tensin Homolog ◽

Tensin Homolog ◽

Endometrial Carcinomas

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.

Download Full-text

Loss of phosphatase activity in PTEN (phosphatase and tensin homolog deleted on chromosome ten) results in endometrial carcinoma in humans: An in-silico study

Heliyon ◽

10.1016/j.heliyon.2019.e03106 ◽

2020 ◽

Vol 6 (1) ◽

pp. e03106 ◽

Cited By ~ 1

Author(s):

Sunil Kanti Mondal ◽

Madhab Kumar Sen

Keyword(s):

Endometrial Carcinoma ◽

Phosphatase Activity ◽

In Silico ◽

Phosphatase And Tensin Homolog ◽

Tensin Homolog ◽

In Silico Study

Download Full-text

Surgical outcome of endoscopic surgery in women with early stage cervical and endometrial carcinoma, the role of surgeon's experience and quality parameters

Geburtshilfe und Frauenheilkunde ◽

10.1055/s-0034-1388268 ◽

2014 ◽

Vol 74 (S 01) ◽

Author(s):

R Mavrova ◽

JC Radosa ◽

S Baum ◽

EF Solomayer ◽

I Juhasz-Böss

Keyword(s):

Endometrial Carcinoma ◽

Endoscopic Surgery ◽

Surgical Outcome ◽

Early Stage ◽

Quality Parameters

Download Full-text

High Throughput Screen Identifies the DNMT1 (DNA Methyltransferase-1) Inhibitor, 5-Azacytidine, as a Potent Inducer of PTEN (Phosphatase and Tensin Homolog)

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.120.314458 ◽

2020 ◽

Vol 40 (8) ◽

pp. 1854-1869

Author(s):

Keith A. Strand ◽

Sizhao Lu ◽

Marie F. Mutryn ◽

Linfeng Li ◽

Qiong Zhou ◽

...

Keyword(s):

Protein Expression ◽

High Throughput ◽

Knockout Mice ◽

Vascular Remodeling ◽

Dna Methyltransferase ◽

Dna Methyltransferase 1 ◽

Protective Effects ◽

High Throughput Screen ◽

Phosphatase And Tensin Homolog ◽

Tensin Homolog

Objective: Our recent work demonstrates that PTEN (phosphatase and tensin homolog) is an important regulator of smooth muscle cell (SMC) phenotype. SMC-specific PTEN deletion promotes spontaneous vascular remodeling and PTEN loss correlates with increased atherosclerotic lesion severity in human coronary arteries. In mice, PTEN overexpression reduces plaque area and preserves SMC contractile protein expression in atherosclerosis and blunts Ang II (angiotensin II)-induced pathological vascular remodeling, suggesting that pharmacological PTEN upregulation could be a novel therapeutic approach to treat vascular disease. Approach and Results: To identify novel PTEN activators, we conducted a high-throughput screen using a fluorescence based PTEN promoter-reporter assay. After screening ≈3400 compounds, 11 hit compounds were chosen based on level of activity and mechanism of action. Following in vitro confirmation, we focused on 5-azacytidine, a DNMT1 (DNA methyltransferase-1) inhibitor, for further analysis. In addition to PTEN upregulation, 5-azacytidine treatment increased expression of genes associated with a differentiated SMC phenotype. 5-Azacytidine treatment also maintained contractile gene expression and reduced inflammatory cytokine expression after PDGF (platelet-derived growth factor) stimulation, suggesting 5-azacytidine blocks PDGF-induced SMC de-differentiation. However, these protective effects were lost in PTEN-deficient SMCs. These findings were confirmed in vivo using carotid ligation in SMC-specific PTEN knockout mice treated with 5-azacytidine. In wild type controls, 5-azacytidine reduced neointimal formation and inflammation while maintaining contractile protein expression. In contrast, 5-azacytidine was ineffective in PTEN knockout mice, indicating that the protective effects of 5-azacytidine are mediated through SMC PTEN upregulation. Conclusions: Our data indicates 5-azacytidine upregulates PTEN expression in SMCs, promoting maintenance of SMC differentiation and reducing pathological vascular remodeling in a PTEN-dependent manner.

Download Full-text