Abstract:Background: To study the expression of PTEN (Phosphatase and Tensin homologue) and Cyclin D1 in normal, hyperplastic and neoplastic endometrium by immunohistochemistry and to corroborate the interrelationship between PTEN and Cyclin D1 in normal to neoplastic endometrial disorders including endometrial carcinoma.Methods: Formalin fixed paraffin embedded (FFPE) sections of spectrum of endometrium in fifty different cases were taken from secretory phase to endometrial carcinoma and subjected to Immunohistochemis… Show more
“…PTEN positivity was found in all 47 (100%) cases of proliferative endometrium, 18 (90%) cases in secretory endometrium, which was similar to several studies in which PTEN positivity was seen in 100% of the cases of proliferative and secretory endometrium. 10,12,13,14,15,16 However , in the study done by Tantbirojn et al 17 , 100% positivity was seen in proliferative endometrium but only 60% in secretory endometrium.…”
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.
“…PTEN positivity was found in all 47 (100%) cases of proliferative endometrium, 18 (90%) cases in secretory endometrium, which was similar to several studies in which PTEN positivity was seen in 100% of the cases of proliferative and secretory endometrium. 10,12,13,14,15,16 However , in the study done by Tantbirojn et al 17 , 100% positivity was seen in proliferative endometrium but only 60% in secretory endometrium.…”
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.
“…Yan et al [25] demonstrated that [42.3%] of their cases exhibited positive expression of Cyclin D1. While Suri et al [32] & Thukral et al [4] detected that [85.71%] of carcinoma endometrium were positive for Cyclin D1.…”
Section: Discussionmentioning
confidence: 99%
“…Endometrial cancer is the most common malignancy of the female genital system. Endometrial carcinoma development involves the stepwise acquisition of several genetic alterations involving oncogenes and tumor suppressor genes [4] . Various prognostic factors have been widely researched to improve the patients' management, treatment, and follow-up.…”
Section: Discussionmentioning
confidence: 99%
“…The presence of many histological subtypes of endometrial carcinoma indicates various tumorigenesis pathways for endometrium cancer development and progression [3], including stepwise attainment of numerous genetic variations in tumor suppressor genes and oncogenes [4] .…”
Section: Introductionmentioning
confidence: 99%
“…Cyclins are key elements in regulating the cell cycle in combination with their respective cyclin-dependent kinases CDK4 and CDK6, which phosphorylate retinoblastoma protein contribute to release of proteins E2F. These proteins can motivate genes mandatory for the cell's progression to the S-phase in the G1-phase [4] .…”
Background: Cyclin D1, a positive regular of the cell cycle, may lead to uncontrolled cell proliferation. The overexpression of Cyclin D1 has been associated with numerous tumors' diagnosis and prognosis. PIN1 binds and isomerizes the phosphorylated serine/threonine-proline motif, which leads to alteration in the structure and function of proteins. The altered phosphorylated proteins by PIN1 are closely linked to cancer development. PIN1 is strongly expressed in most tumors, suggesting it promotes tumorigenesis and is negatively associated with the clinical prognosis. Objectives: To assess Cyclin D1 & PIN1 expression and correlation in endometrial adenocarcinoma. Also, to assess the relationship between Cyclin D1 & PIN1 expression and clinicopathological variables of cases with endometrial carcinoma. Materials and Methods: The study included 30 cases of endometrial adenocarcinoma specimens. Immunohistochemical staining was performed for both Cyclin D1 and PIN1. Blocks of tumor tissue and clinical data were gathered from Pathology Department of Al-Zahraa University Hospital files between July 2017 and October 2019. Results: Cyclin D1 positive expression and PIN1 high expression were increased significantly with age, high clinicalstage, high pathological grade, and more myometrium invasion depth. Cyclin D1 expression was positively associated with PIN1 expression (P-value = 0.004). Conclusions: Cyclin D1 and PIN1 expression are associated with age, stage, grade, and depth of myometrial wall invasion in patients with endometrial carcinoma. The overexpression of Cyclin D1 & PIN1 seems to indicate a more malignant phenotype of endometrial carcinoma.
Background: Atypical endometrial hyperplasia is generally considered as a precursor lesion of endometrial
carcinoma. PTEN gene is the most commonly mutated gene in endometrial carcinoma as well as its precursor lesions.
Objective: To study the prevalence of endometrial hyperplasia and carcinoma and also to determine the level of PTEN
gene expression in normal, hyperplastic and neoplastic endometrium. This cross-sectional Material and Methods:
study included 150 endometrial biopsy and hysterectomy specimen over two years duration. Patient's age,marital
status,parity,bodyweight,duration of symptoms and history of exogenous estrogen therapy were taken.Specimens
received in 10% buffered formalin were processed, slides prepared and routine haematoxylin and eosin(H & E) and
PTEN immunostaining were done. Endometrial hyperplasia and endometrial carcinoma were seen in 41-50 Results:
years age group. Maximum number of cases were seen in nulliparous women who presented with abnormal uterine
bleeding.Loss of PTEN expression was observed in 22.2% of atypical endometrial hyperplasia and all cases of
carcinoma. PTEN immunostaining should be done in all cases of endometrial hyperplasia to detect pre Conclusion: -
malignant lesion which are likely to progress to carcinoma.
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