Bcl‐2, iNOS, p53 and PCNA expression in normal, disordered proliferative, hyperplastic and malignant endometrium

Cinel, Leyla; Polat, Ayşe; Aydın, Özlem; Düşmez, Duygu; Eğılmez, Reyhan

doi:10.1046/j.1440-1827.2002.01358.x

Cited by 23 publications

(14 citation statements)

References 29 publications

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“…35 Cinel et al reported that p53 positivity was not determined in normal endometria outside a few tubal metaplasia areas. 36 Our results were also similar. The metaplastic cells of anovulatory DUB causes may simulate endometrial hyperplasia and endometrial adenocarcinoma, leading to difficulty in cytologic interpretation.…”

Section: Endometrial Immunocytochemistrysupporting

confidence: 80%

Utility of thin‐layer preparations in endometrial cytology: Immunocytochemical expression of PTEN, beta‐catenin and p53 for benign endometrial lesions

Norimatsu

Miyamoto

Kobayashi

et al. 2008

Diagnostic Cytopathology

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This article focuses on the characteristic features of morphology and molecular biology of PTEN, beta-catenin, and p53 immunocytochemistry in normal endometrium (proliferative, secretory, and atrophic) and endometrial glandular and stromal breakdown (EGBD) using thin-layer specimens. During a 6-month period, 120 endometrial samples were collected directly using the Uterobrush and a thin-layer specimen was prepared. Immunocytochemical expression of PTEN, beta-catenin, and p53 were investigated using 30 cases each of proliferative endometrium (PE), secretory endometrium (SE), atrophic endometrium (AE), and EGBD.PTEN expression of normal endometrial glandular epithelial cells changes with the hormonal status; PE produce very high expression, SE creates attenuation or disappearance of PTEN expression and AE diminished more in comparison with SE. PTEN expression of EGBD showed a tendency towards attenuation compared with PE, but showed high expression in comparison with SE and AE. As for the immunoreactivity of beta-catenin, in all phases (PE, SE, AE, and EGBD), it was observed in the cytoplasm of glandular epithelial cells, but not nuclei, and showed strong membranous staining. As for the p53 immunoreactivity, p53 positivity was not observed in the glandular epithelial cells in all phases (PE, SE, AE, and EGBD) with the exception of some metaplastic cells. The presence of p53 immunoreactivity of a weak, low ratio in metaplastic cells was unexpected. In the current study, the expression manner of PTEN, beta-catenin, and p53 immunocytochemistry was observed in the normal endometrium (PE, SE, and AE) and EGBD.

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Section: Endometrial Immunocytochemistrysupporting

confidence: 80%

Utility of thin‐layer preparations in endometrial cytology: Immunocytochemical expression of PTEN, beta‐catenin and p53 for benign endometrial lesions

Norimatsu

Miyamoto

Kobayashi

et al. 2008

Diagnostic Cytopathology

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“…Altogether 20 observational studies with a total of 1,278 specimens (137 proliferative endometrium, 676 endometrial hyperplasia, and 465 endometrial cancer), were included in the systematic review. The flow diagram reporting the process of study selection is shown in Figure .…”

Section: Resultsmentioning

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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“…In head and neck cancer, excessive NO correlates with cancer risk and metastatic potential (52, 108,109), and in colorectal cancer increased NO leads to enhanced angiogenesis and invasiveness (110,111). Elevated NO concentrations have also been correlated with endometrial, cervical and gastric cancers, and tumors of the central nervous system (112)(113)(114)(115)(116)(117)(118). For these conditions, however, there is currently no targeted approach for intervention of NO production available for clinical use.…”

Section: The Dual Role Of Nitric Oxide In Cancermentioning

confidence: 99%

Inhibition of Dimethylarginine Dimethylaminohydrolase (DDAH) Enzymes as an Emerging Therapeutic Strategy to Target Angiogenesis and Vasculogenic Mimicry in Cancer

et al. 2020

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The small free radical gas nitric oxide (NO) plays a key role in various physiological and pathological processes through enhancement of endothelial cell survival and proliferation. In particular, NO has emerged as a molecule of interest in carcinogenesis and tumor progression due to its crucial role in various cancer-related events including cell invasion, metastasis, and angiogenesis. The dimethylarginine dimethylaminohydrolase (DDAH) family of enzymes metabolize the endogenous nitric oxide synthase (NOS) inhibitors, asymmetric dimethylarginine (ADMA) and monomethyl arginine (L-NMMA), and are thus key for maintaining homeostatic control of NO. Dysregulation of the DDAH/ADMA/NO pathway resulting in increased local NO availability often promotes tumor growth, angiogenesis, and vasculogenic mimicry. Recent literature has demonstrated increased DDAH expression in tumors of different origins and has also suggested a potential ADMA-independent role for DDAH enzymes in addition to their well-studied ADMA-mediated influence on NO. Inhibition of DDAH expression and/or activity in cell culture models and in vivo studies has indicated the potential therapeutic benefit of this pathway through inhibition of both angiogenesis and vasculogenic mimicry, and strategies for manipulating DDAH function in cancer are currently being actively pursued by several research groups. This review will thus provide a timely discussion on the expression, regulation, and function of DDAH enzymes in regard to angiogenesis and vasculogenic mimicry, and will offer insight into the therapeutic potential of DDAH inhibition in cancer based on preclinical studies.

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Bcl‐2, iNOS, p53 and PCNA expression in normal, disordered proliferative, hyperplastic and malignant endometrium

Cited by 23 publications

References 29 publications

Utility of thin‐layer preparations in endometrial cytology: Immunocytochemical expression of PTEN, beta‐catenin and p53 for benign endometrial lesions

Utility of thin‐layer preparations in endometrial cytology: Immunocytochemical expression of PTEN, beta‐catenin and p53 for benign endometrial lesions

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

Inhibition of Dimethylarginine Dimethylaminohydrolase (DDAH) Enzymes as an Emerging Therapeutic Strategy to Target Angiogenesis and Vasculogenic Mimicry in Cancer

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