Study of prognostic and diagnostic significance of P53 and PTEN mutation in proliferative lesions of endometrium.

2020 ◽  
Vol 3 (08) ◽  
Author(s):  
Dr. Suchandra Ray ◽  
Dr. Ashish Jha ◽  
Dr. Ayesha Afreen Islam ◽  
Dr. Moumita Sengupta
Keyword(s):  
Endometrial Carcinoma ◽  
Endometrial Hyperplasia ◽  
Premalignant Lesions ◽  
Pten Gene ◽  
P Value ◽  
Diagnostic Significance ◽  
P53 Expression ◽  
Chromosome 17P13 ◽  
Endometrioid Endometrial Carcinoma ◽  
Endometrial Carcinomas

Background: Endometrial hyperplasia essentially implies an overgrowth of the endometrium. Complex hyperplasia associated with cellular atypia, seems to be the most important predictor of malignant potential. Endometrioid Endometrial Carcinomas account for three-fourths of Endometrial Carcinomas and are thought to develop following a continuum of premalignant lesions ranging from endometrial hyperplasia without atypia, to hyperplasia with atypia, and finally to well-differentiated carcinoma. Currently the most frequently observed gene mutation in endometrioid carcinoma is located on chromosome 10 and is related with the PTEN gene (phoshatase and tensin homolog). PTEN inactivation is found to correlate with clonal growth pattern detected in endometrial hyperplasia and carcinoma. The p53 tumor suppressor gene locates to chromosome 17p13. The abnormal p53 expression has been found in 11% of grade 1 endometrioid endometrial carcinoma, while p53 mutations occur in 90% of non-endometrioid endometrial carcinoma. Aims and objectives: In this study we aim to evaluate the immuno histochemical expression of P53 and PTEN genes in endometrial hyperplasia and endometrial carcinoma and correlate their expression with prognostic outcomes like grade and stage, in cases of endometrial carcinoma. Material and methods: A prospective study of 60 patients with abnormal uterine bleed in the peri and post menopausal age was conducted, for a period of three years. Histological specimens were studied for HPE and IHC for the markers PTEN and P53. Results: The mean age for hyperplastic and carcinomatous lesions was 44.9 years and 53.2 years respectively. 35% (21 cases) were endometrial hyperplasia and 65% (39 cases) of cases were endometrial carcinoma. Among endometrial carcinoma 87% are of endometrioid type and 13% are of other types, which include serous, clear and malignant mixed Mullerian type of carcinoma. IHC study showed that PTEN expression is higher in endometrial hyperplasia than endometrial carcinoma cases. Elevated P53 expression correlated with poor differentiation of endometrial cancer. P53 was found to be more in cases with FIGO staging III &IV compared to stage I & II (100% vs 18.1% p value= 0.0016) and grade 3 compared to grade 1&2 (50% vs 0 p value= 0.0116).   Conclusion: Immuno histochemical biomarkers like PTEN and P53 may contribute to better tumor characterization and thus more precisely determine its clinical behavior.  Key words: endometrial hyperplasia, endometrial carcinoma, PTEN, P53.

Endometrioid Endometrial Carcinoma With Spindle Cells–Aberrant p16 and p53 Expression

2018 ◽  
Vol 27 (2) ◽  
pp. 203-207
Author(s):  
Snehal Sonawane ◽  
Osama Elfituri ◽  
Yanmin Zhang ◽  
Edgardo Yordan ◽  
Nicholas Ree
Keyword(s):  
Endometrial Carcinoma ◽  
Spindle Cell ◽  
Tumor Type ◽  
Immunohistochemical Expression ◽  
Cell Component ◽  
Diagnostic Dilemma ◽  
P53 Overexpression ◽  
P53 Expression ◽  
Spindle Cells ◽  
Endometrioid Endometrial Carcinoma

Endometrioid carcinoma is known for its diverse morphology and may pose a diagnostic dilemma when it presents with a spindle cell component. We present a case of a 65-year-old woman with postmenopausal bleeding. Physical examination showed a mass protruding from the external cervical os. The patient underwent biopsy followed by hysterectomy. Pathologic examination showed an endometrioid endometrial carcinoma with spindle cell differentiation arising in an endometrial polyp, which raised a variety of differential diagnoses. Prior reports of this tumor type showed nonaberrant immunohistochemical expression of p16 and p53. However, this case showed p16 and p53 overexpression indicating that there is a spectrum of these tumors.

scholarly journals Myoinvasive Pattern as a Prognostic Marker in Low-Grade, Early-Stage Endometrioid Endometrial Carcinoma

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1845 ◽  
Author(s):  
Ignacio Ruz-Caracuel ◽  
Jorge L Ramón-Patino ◽  
Álvaro López-Janeiro ◽  
Laura Yébenes ◽  
Alberto Berjón ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Microsatellite Instability ◽  
Endometrial Carcinoma ◽  
Early Stage ◽  
Disease Free Survival ◽  
Figo Stage ◽  
Low Grade ◽  
Gynecology And Obstetrics ◽  
Endometrioid Endometrial Carcinoma ◽  
Endometrial Carcinomas

Low-grade and early Federation for Gynecology and Obstetrics (FIGO) stage endometrioid endometrial carcinomas (EEC) have an excellent prognosis. However, approximately 10% of patients develop recurrence, which cannot be correctly predicted at diagnosis. We evaluated myoinvasive patterns as a prognostic factor of relapse in low-grade, early-stage EEC. Two-hundred and fifty-eight cases were selected according to the following inclusion criteria: (i) endometrioid endometrial carcinomas, (ii) grade 1 or 2 with (iii) FIGO stage I or II, and (iv) clinical follow-up. Slides were reviewed to annotate the myoinvasive pattern present in each case (infiltrative glands, microcystic, elongated and fragmented –MELF-, broad front, adenomyosis-like and adenoma malignum). Microsatellite instability was studied by immunoexpression of mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6). There were 29 recurrences (11.2%) among the 258 cases analysed. A predominant broad front myoinvasive pattern was significantly associated with tumour relapse (p = 0.003). The presence of a pattern of infiltrative glands (p = 0.001) and microsatellite instability (p = 0.004) were associated with lower disease-free survival, without having an impact on overall survival. Our observations suggest the potential value of the pattern of myoinvasion as a prognostic factor in low-grade, early-stage endometrioid endometrial carcinoma.

Expression of p27 and p53: comparative analysis of uterine carcinosarcoma and endometrial carcinoma

2004 ◽  
Vol 14 (2) ◽  
pp. 354-359 ◽  
Author(s):  
A. Abargel ◽  
I. Avinoach ◽  
V. Kravtsov ◽  
M. Boaz ◽  
M. Glezerman ◽  
...  
Keyword(s):  
Endometrial Carcinoma ◽  
Immunohistochemical Staining ◽  
Endometrioid Carcinoma ◽  
Uterine Carcinosarcoma ◽  
Clinical Value ◽  
P53 Overexpression ◽  
P53 Expression ◽  
Epithelial Component ◽  
Endometrial Carcinomas ◽  
Epithelial Element

The aim of the study was to assess both p27 and p53 expression in the stromal and epithelial component of carcinosarcoma and to assess if their expression in the latter is different than in endometrial carcinoma. Immunohistochemical staining for p27 and p53 was performed on paraffin-embedded tissue blocks of 18 uterine specimens with carcinosarcoma and their expression assessed. Their expression in the epithelial element was also compared to that in 35 paraffin-embedded tissue blocks of endometrial endometrioid carcinoma.Reduced p27 expression was observed in a similarly high proportion of the stromal (77.8%) as well as of the epithelial component (66.7%) of carcinosarcoma. Although statistically not significant, the proportion of reduced p27 expression in endometrial carcinoma (85.7%) was higher than in the epithelial element of carcinosarcoma.The percentage of p53 overexpression in both elements of carcinosarcomas and in endometrial carcinomas was low and also similar (27.8 and 20.0%, respectively).Our results indicate that reduced p27 expression is common and p53 overexpression is infrequent in carcinosarcoma. Their similar rates of expression in the stromal and epithelial elements of the tumor support the contention of a monoclonal origin of carcinosarcoma. Unexpectedly, reduced p27 expression is more common in endometrial carcinoma than in the epithelial element of carcinosarcoma, in spite of the less favorable prognosticators and outcome in the latter.Further studies of p27 expression in carcinosarcoma are indicated to establish its clinical value in this aggressive malignancy.

scholarly journals ALDH1 expression predicts progression of premalignant lesions to cancer in Type I endometrial carcinomas

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vei Mah ◽  
Yahya Elshimali ◽  
Alison Chu ◽  
Neda A. Moatamed ◽  
Jamar P. Uzzell ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Endometrial Hyperplasia ◽  
Prognostic Indicator ◽  
Premalignant Lesions ◽  
Stem Cell Marker ◽  
Type I ◽  
Clinical Value ◽  
Aldh1 Expression ◽  
Estrogen Stimulation ◽  
Endometrial Carcinomas

AbstractIn type 1 endometrial cancer, unopposed estrogen stimulation is thought to lead to endometrial hyperplasia which precedes malignant progression. Recent data from our group and others suggest that ALDH activity mediates stemness in endometrial cancer, but while aldehyde dehydrogenase 1 (ALDH1) has been suggested as a putative cancer stem cell marker in several cancer types, its clinical and prognostic value in endometrial cancer remains debated. The aim of this study was to investigate the clinical value of ALDH1 expression in endometrial hyperplasia and to determine its ability to predict progression to endometrial cancer. Interrogation of the TCGA database revealed upregulation of several isoforms in endometrial cancer, of which the ALDH1 isoforms collectively constituted the largest group. To translate its expression, a tissue microarray was previously constructed which contained a wide sampling of benign and malignant endometrial samples. The array contained a metachronous cohort of samples from individuals who either developed or did not develop endometrial cancer. Immunohistochemical staining was used to determine the intensity and frequency of ALDH1 expression. While benign proliferative and secretory endometrium showed very low levels of ALDH1, slightly higher expression was observed within the stratum basalis. In disease progression, cytoplasmic ALDH1 expression showed a step-wise increase between endometrial hyperplasia, atypical hyperplasia, and endometrial cancer. ALDH1 was also shown to be an early predictor of EC development, suggesting that it can serve as an independent prognostic indicator of patients with endometrial hyperplasia with or without atypia who would progress to cancer (p = 0.012).

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

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.

Assessment of lymphovascular invasion in early stage endometrial carcinoma -a retrospective study

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ambreen Moatasim ◽  
Zujajah Hameed ◽  
Imran Ahmad
Keyword(s):  
Retrospective Study ◽  
Endometrial Carcinoma ◽  
Lymphovascular Invasion ◽  
Early Stage ◽  
Tumor Grade ◽  
Adjuvant Radiation ◽  
Inclusion Criteria ◽  
Future Studies ◽  
Endometrioid Endometrial Carcinoma ◽  
Endometrial Carcinomas

Abstract Introduction Endometrial carcinoma is associated with several known prognostic factors. Recently, lymphovascular invasion (LVI) has gained a prominent position in the risk assessment of early endometrioid endometrial carcinoma, in identifying patients who can benefit from adjuvant radiation therapy. This study aims to assess LVI in early-stage endometrioid endometrial carcinoma accurately with emphasis on its extent /grading. We also propose a few local recommendations for improving LVI reproducibility in endometrial carcinoma to guide future studies. Methods The duration of this retrospective study was 2 years. Early-stage I (Ia and Ib), and grade 1 and 2 endometrioid endometrial carcinomas were included. 03 reviewers independently recorded their findings on H&E stained slides. LVI was graded as none, focal and substantial. In discordant cases, immunohistochemical stain CD 31 was used. All the data was entered in the statistical software SPSS version 26 and analyzed for frequencies. The relationships between various histological parameters assessed and the degree of reproducibility for LVI amongst various observers were also determined. Results Out of a total of 70 cases of endometrioid carcinoma diagnosed on hysterectomy specimen, only 32 met our inclusion criteria. The rate of LVI positivity was 6.3 %, 34.4 %, and 37.5 % respectively for reviewers 1, 2, and 3. The degree of reproducibility in LVI assessment and LVI grading was significant amongst reviewers 2 and 3. Also, a significant association was drawn between tumor grade and LVI. Conclusion Despite limitations in our study we recommend including both LVI assessment and grading in routine reporting formats locally. By adding a second reviewer in LVI assessment and using CD31 in discrepant cases LVI positivity can be significantly increased.

scholarly journals Value of p53 and estrogen receptors immunohistochemical staining in endometrial carcinoma

2019 ◽  
Vol 8 (12) ◽  
pp. 4885
Author(s):  
Dejan Opric ◽  
Amer Suskic ◽  
Sanela Halilovic Suskic ◽  
Gorana Nikolic ◽  
Isidora Filipovic
Keyword(s):  
Estrogen Receptors ◽  
Endometrial Carcinoma ◽  
Diagnostic Value ◽  
Public Hospitals ◽  
Lower Grade ◽  
High Grade ◽  
P53 Expression ◽  
Study Population ◽  
Grade Ii ◽  
Endometrial Carcinomas

Background: Since there are many articles dealing with estimating prognostic and diagnostic value of ER and p53, using different, usually complex ICH interpretation methods, we wanted to evaluate significance of p53 and ER ICH positivity in endometrial carcinoma, using easily applicable criteria that would help pathologists and clinicians to be sure in ICH findings noted in the report.Methods: This paper deals with data of the patients treated for endometrial carcinoma in Public Hospitals in Travnik, gynecological department in the period from 1st January 2013 to 1st January 2019. The study included 97 women with endometrial carcinoma, with ages ranging from 42 to 90 years (mean of 64 years). Sample consisted of 72 cases (74.2%) of endometrioid and 25 cases (25.8%) of non-endometrioid carcinoma.Results: p53 expression was observed in 13.8% carcinomas of the endometrioid type and in 68% carcinomas of non-endometrioid type, while estrogen receptors were more frequently observed in tumors of the endometrioid type (61%) in contrast to non-endometrioid type (28%). Among 72 cases, those with grade I expressed estrogen receptors (26 out of 34 cases - 72%) more frequently than those with grades II and III. Frequency of p53 positivity was significantly higher at higher grades (grade I - 5.8%, grade II - 11.5%, grade III - 71.4%). Stage I carcinomas showed p53 staining less frequently (22.2%) that carcinomas diagnosed at later stages (31.5%).Conclusions: Using 80% nuclei stained as threshold for p53 positivity, we concluded that p53 is marker of high-grade endometrial carcinomas: high grade endometrioid and non-endometrioid carcinomas. Using 1% of cells as threshold for ER positivity, we confirmed that ER are common in endometrioid type carcinoma, in contrast to non-endometrioid type. Although observed, higher frequency of ER in tumors with lower grade and stage was not statistically confirmed in our study population.

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