Epigenetic and genetic landscape of uterine leiomyomas: a current view over a common gynecological disease

Laganà, Antonio Simone; Vergara, Daniele; Favilli, Alessandro; Rosa, Valentina Lucia La; Tinelli, Andrea; Gerli, Sandro; Noventa, Marco; Vitagliano, Amerigo; Triolo, Onofrio; Rapisarda, Agnese Maria Chiara; Vitale, Salvatore Giovanni

doi:10.1007/s00404-017-4515-5

Cited by 126 publications

(91 citation statements)

References 109 publications

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“…Nonetheless, hysteroscopy plays a crucial role in the most challenging topics of women's health, from infertility diagnostic work-up [7,8] to post-menopausal abnormal uterine bleeding and uterine pathologies [9,10]. Currently, available technologies allow one to perform several diagnostic and operative procedures without the need for anesthesia and without any pain or distress for the patient [11,12]. For this reason, the role of dilatation and curettage to assess intrauterine pathologies and abnormal uterine bleeding tends to be no higher than office hysteroscopy [13].…”

Section: Introductionmentioning

confidence: 99%

Concordance between the Hysteroscopic Diagnosis of Endometrial Hyperplasia and Histopathological Examination

et al. 2019

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The goal of this paper is to assess the concordance between the clinical diagnosis of Endometrial Hyperplasia (EH), suspected by senior gynecologists throughout outpatient office hysteroscopy, and the results from histopathological examination, in order to evaluate hysteroscopic accuracy for EH. A prospective cohort study was done at a Tertiary University Hospital. From January to December 2018, we enrolled women with the following criteria: abnormal uterine bleeding in post-menopause and endometrial thickening in pre-or post-menopause. Patients underwent office hysteroscopy with a 5 mm continuous-flow hysteroscope, and endometrial biopsies were taken using miniaturized instruments. Senior operators had to foresee histopathological diagnosis using a questionnaire. Histopathological examination was conducted to confirm the diagnosis. This study was approved by the local ethical and registered in the ClinicalTrials.gov registry (ID no. NCT03917147). In 424 cases, 283 clinical diagnoses of EH were determined by senior surgeons. A histopathological diagnosis was then confirmed in 165 cases (58.3%; p = 0.0001). Furthermore, 14 endometrial carcinoma and atypical hyperplasia were found. The sensitivity, positive predictive value, and negative predictive values for EH were, respectively, 90.4, 58.4, and 86.6%. Subdivided by clinical indication, the sensitivity was higher in patients with post-menopause endometrial thickening. The diagnostic accuracy of office hysteroscopy in the diagnosis and prediction of endometrial hyperplasia was high. Senior operators could foresee EHs in more than half the cases.

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Section: Introductionmentioning

confidence: 99%

Concordance between the Hysteroscopic Diagnosis of Endometrial Hyperplasia and Histopathological Examination

et al. 2019

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“…In our study, PRa showed to be significantly unregulated in myoma of PreM compared to myoma of PostM women, which showed to be same in myometrium tissue ( Figure 1G, 3G). Those finding correlate with the fact that progesterone is cyclically elevated during the reproductive years, are significantly elevated during pregnancy, and are suppressed after menopause, however it is still very difficult to distinguishing the relative importance of estrogen versus progesterone [22,23].…”

Section: Discussionmentioning

confidence: 96%

The influence of the expression of steroid receptors on angiogenesis, proliferation and apoptosis in myomas of pre- and postmenopausal women

et al. 2019

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Introduction/Objective The aim of this study was to determine the effects of the estrogen and progesterone receptor status on angiogenesis, proliferation, and apoptosis of myoma cells in premenopausal (PreM) and postmenopausal (PostM) women. Methods This was a cross section; clinical-experimental, retrospective, non-interventional study in the field of the study of fundamental pathogenesis mechanisms of disease using pathohistological materials from the existing archive. The research included 76 patients diagnosed with uterine leiomyomas, operatively treated in the Clinic for Gynecology and Obstetrics, Clinical Centre Kragujevac, Serbia. According to the menstrual status, we formed two experimental subgroups. The first group was PreM women (n = 35; 46.2 ± 5.02 years old), and the second group was PostM women (n = 41; 60.25 ± 5.41 years old). Hematoxylin-eosin staining for myoma and myometrium was conducted, as well as immunohistochemistry for ERα, ERβ, PRа, vascular endothelial growth factor, endoglin, Ki67, and caspase-3. Results Progesterone receptor was overexpressed in myoma and myometrium of PreM compared to myoma and myometrium of PostM women. Expression of caspase-3 was a statistically significant increase in PostM women compared to PreM group. ERα and ERβ were not changed among groups neither in myoma nor in myometrium samples. Conclusion According to our data, PRа had higher influence on apoptosis and cell growth than estrogen receptors. Since PRа was increased in PreM in both myoma and myometrium, probably this expression led further to lower expression of apoptotic marker in PreM women.

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“…Genetic defects are known to be the key points in tumor formation and a great amount of data has recently accumulated in this field. UF's cells contain multiple gene alterations that differentiate them from normal uterine muscle cells [23]. As in many other cases, a possible functional role of promoter deoxyribonucleic acid (DNA) methylation-mediated gene silencing has been proposed in the pathogenesis of those tumors [24].…”

Section: Uterine Fibroids-introduction Into Geneticsmentioning

confidence: 99%

The Role of miRNA and Related Pathways in Pathophysiology of Uterine Fibroids—From Bench to Bedside

Ciebiera

Włodarczyk

Zgliczyński

et al. 2020

IJMS

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Uterine fibroids (UFs) are the most common benign tumors of the female genital tract. Their prevalence usually is estimated at 30–40%, but may reach up to 70–80% in predisposed groups of women. UFs may cause various clinical issues which might constitute the major reason of the overall deterioration of the quality of life. The mechanisms leading to UFs formation and growth still remain poorly understood. The transformation of smooth muscle cells of the uterus into abnormal, immortal cells, capable of clonal division, is thought to be a starting point of all pathways leading to UF formation. Micro-ribonucleic acids (miRNAs) are non-coding single-stranded RNAs about 22 nucleotides in length, that regulate gene expression. One of recent advances in this field is the comprehension of the role of miRNAs in tumorigenesis. Alterations in the levels of miRNAs are related to the formation and growth of several tumors which show a distinct miRNA signature. The aim of this review is to summarize the current data about the role of miRNAs in the pathophysiology of UFs. We also discuss future directions in the miRNA research area with an emphasis on novel diagnostic opportunities or patient-tailored therapies. In our opinion data concerning the regulation of miRNA and its gene targets in the UFs are still insufficient in comparison with gynecological malignancies. The potential translational use of miRNA and derived technologies in the clinical care is at the early phase and needs far more evidence. However, it is one of the main areas of interest for the future as the use of miRNAs in the diagnostics and treatment of UFs is a new and exciting opportunity.

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Epigenetic and genetic landscape of uterine leiomyomas: a current view over a common gynecological disease

Abstract: The new clues on genetics and epigenetics, as well as about the growth factors that control normal and pathological myometrial cellular biology may be of great help for the development of new effective and less invasive therapeutic strategies in the near future.

Cited by 126 publications

References 109 publications

Concordance between the Hysteroscopic Diagnosis of Endometrial Hyperplasia and Histopathological Examination

Concordance between the Hysteroscopic Diagnosis of Endometrial Hyperplasia and Histopathological Examination

The influence of the expression of steroid receptors on angiogenesis, proliferation and apoptosis in myomas of pre- and postmenopausal women

The Role of miRNA and Related Pathways in Pathophysiology of Uterine Fibroids—From Bench to Bedside

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