Endometrial Polyps and Benign Endometrial Hyperplasia Have Increased Prevalence of DNA Fragmentation Factors 40 and 45 (DFF40 and DFF45) Together With the Antiapoptotic B-Cell Lymphoma (Bcl-2) Protein Compared With Normal Human Endometria

Banaś, Tomasz; Pityński, Kazimierz; Mikoś, Marcin; Cielecka-Kuszyk, Joanna

doi:10.1097/pgp.0000000000000442

Cited by 13 publications

(8 citation statements)

References 31 publications

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“…As Bcl‐2 expression may not decrease simultaneously in glands and stroma it would be interesting to study the possible relevance of Bcl‐2 stromal expression in the differential diagnosis of endometrial hyperplasia. Nevertheless, given the recent discoveries on the genetics of endometrial cancer, the need for a molecular definition of endometrial neoplastic specimens has been growing, as well as the search for cheaper immunohistochemical surrogates of genetic prognostic markers .…”

Section: Discussionmentioning

confidence: 99%

Loss of B‐cell lymphoma 2 immunohistochemical expression in endometrial hyperplasia: A specific marker of precancer and novel indication for treatment

Travaglino

Raffone

Saccone

et al. 2018

Acta Obstet Gynecol Scand

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Abbreviations: AUC, area under the curve; EIN, endometrial intraepithelial neoplasia; LR-, negative likelihood ratio; LR+, positive likelihood ratio; OR, odds ratio; WHO, World Health Abstract Introduction: Endometrial hyperplasia is differentiated into benign or premalignant. Two histological classifications are used for this purpose: World Health Organization (WHO) classification, based on cytological atypia, disregarding glandular complexity, and endometrial intraepithelial neoplasia (EIN) classification, based on several different parameters. B-cell lymphoma 2 (Bcl-2) loss has been studied as immunohistochemical marker with the aim of improving the differential diagnosis between benign and premalignant hyperplasia. We aimed to evaluate: (A) Bcl-2 loss as marker of endometrial precancer, by assessing it in proliferative endometrium, benign hyperplasia, premalignant hyperplasia, and endometrial cancer; (B) the diagnostic accuracy of Bcl-2 in the differential diagnosis between benign and premalignant endometrial hyperplasia; (c) how the results change according to the histological classification and the thresholds of Bcl-2 expression used. Material and methods: Electronic databases were searched from their inception to March 2018. All studies assessing Bcl-2 immunohistochemistry in endometrial specimens were included.Results: In total, 20 observational studies assessing 1,278 specimens were included.Bcl-2 loss rates were not significantly different between proliferative endometrium and benign hyperplasia (P = 0.12) and between premalignant hyperplasia and endometrial cancer (P = 0.53). Among hyperplasias, Bcl-2 loss was significantly associated with premalignancy, according to both the WHO (OR = 4.39; P < 0.00001) and EIN classifications (OR = 6.07; P = 0.01), and also with architecture complexity (OR = 2.06; P = 0.02). Using the WHO classification, Bcl-2 loss showed low diagnostic accuracy in detecting premalignant hyperplasia (area under the curve [AUC] = 0.708), with a sensitivity of 0.41, a specificity of 0.81, a positive likelihood ratio of 3.22, and a negative likelihood ratio of 0.69. Using the EIN classification, accuracy was high (AUC = 0.938), K E Y W O R D S apoptosis, biomarker, cancer, endometrial hyperplasia, neoplasia Key messageUsing endometrial intraepithelial neoplasia criteria, B-cell lymphoma 2 (Bcl-2) loss is a highly specific and accurate marker of endometrial precancer. Bcl-2 loss in endometrial hyperplasia may be a novel indication for treatment.

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Section: Discussionmentioning

confidence: 99%

Loss of B‐cell lymphoma 2 immunohistochemical expression in endometrial hyperplasia: A specific marker of precancer and novel indication for treatment

Travaglino

Raffone

Saccone

et al. 2018

Acta Obstet Gynecol Scand

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“…[18][19][20] Glandular, menopauseindependent AB DNA fragmentation factor 40, 45 (DFF40), (DFF45) and Bcl-2 overexpression may play an important role in the pathogenesis of endometrial polyps. 21 Ki67 expression was observed to occur predominately in the proliferative phase, with glandular epithelium exhibiting the strongest expression. Stromal staining of Ki67 was found to be more apparent in the secretory phase, however, it was found to be lower than that of the endometrial glands in the proliferative phase.…”

Section: Aetiology and Pathogenesismentioning

confidence: 94%

“…18–20 Glandular, menopause-independent AB DNA fragmentation factor 40, 45 (DFF40), (DFF45) and Bcl-2 overexpression may play an important role in the pathogenesis of endometrial polyps. 21…”

Section: Aetiology and Pathogenesismentioning

confidence: 99%

Endometrial polyps: Pathogenesis, sequelae and treatment

et al. 2019

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Endometrial polyps are overgrowths of endometrial glands that typically protrude into the uterine cavity. Endometrial polyps are benign in nature and affect both reproductive age and postmenopausal women. Although endometrial polyps are relatively common and may be accompanied by abnormally heavy bleeding at menstruation. In asymptomatic women, endometrial polyps may regress spontaneously, in symptomatic women endometrial polyps can be treated safely and efficiently with hysteroscopic excision.

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“…Bcl-2 expression is observed in the normal cycling endometrium and Bcl-2 expression is increased in the polyps compared with that in the endometrium. 20,21 Polyps seem to occur with aberrant endometrium apoptosis. The endometria of endometriosis patients contained significantly higher levels of Bcl-2 proteins than those of patients without endometriosis.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical expression of estrogen receptor α, Bcl‐2 and NF‐κB P65 in the polyps of patients with and without endometriosis

Jiang

Yang

Huang

et al. 2020

J of Obstet and Gynaecol

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Aim To compare the expression of estrogen receptor α (ERα), Bcl‐2 and NF‐κB P65 in endometrial polyps from patients with and without endometriosis. Methods Immunohistochemistry was used to characterize the expression of ERα, Bcl‐2 and NF‐κB P65 in proliferative phase endometrial polyps from patients with and without endometriosis. H‐Scores indicating the staining intensity for ERα, Bcl‐2 and NF‐κB P65 in the glandular epithelium and stroma were measured separately. Apoptotic cells were detected with the use of the dUTP nick‐end labeling (TUNEL) assay. Results Bcl‐2 was expressed in the cytoplasm of glandular epithelial cells, whereas ERα was expressed in the nuclei of both glandular epithelial and stromal cells. NF‐κB P65 was observed in the cytoplasm of both glandular epithelial and stromal cells. The H‐scores for Bcl‐2 in the endometrial glands significantly higher in the endometriosis polyp group than in the non‐endometriosis polyp group. The H‐scores for ERα in both stromal and glandular epithelial cells were significantly higher in the endometriosis polyp group than in the non‐endometriosis polyp group. The H‐scores for Bcl‐2 and ERα were positively correlated in all of the women examined. Apoptotic cells in the endometriosis polyp group were significantly less than that of the non‐endometriosis polyp group. Conclusion There expression levels of Bcl‐2 and ERα, both of which were significantly increased in the polyps of endometriosis patients compared to those of patients without endometriosis, were positively correlated. These results suggested that imbalanced apoptosis secondary to abnormally high ERα expression was responsible for the high prevalence of polyps in endometriosis patients.

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Endometrial Polyps and Benign Endometrial Hyperplasia Have Increased Prevalence of DNA Fragmentation Factors 40 and 45 (DFF40 and DFF45) Together With the Antiapoptotic B-Cell Lymphoma (Bcl-2) Protein Compared With Normal Human Endometria

Cited by 13 publications

References 31 publications

Loss of B‐cell lymphoma 2 immunohistochemical expression in endometrial hyperplasia: A specific marker of precancer and novel indication for treatment

Loss of B‐cell lymphoma 2 immunohistochemical expression in endometrial hyperplasia: A specific marker of precancer and novel indication for treatment

Endometrial polyps: Pathogenesis, sequelae and treatment

Immunohistochemical expression of estrogen receptor α, Bcl‐2 and NF‐κB P65 in the polyps of patients with and without endometriosis

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