Etiology, Diagnosis, and Management of Uterine Leiomyomas

Rice, Kate E.; Secrist, Jenny R.; Woodrow, Elizabeth L.; Hallock, Laura M.; Neal, Jeremy L.

doi:10.1111/j.1542-2011.2012.00176.x

Cited by 31 publications

(37 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Benign breast disease and endometriosis, along with uterine fibroids, are diagnosed most frequently among reproductive-age women (12, 13) and have also been associated with hormone-related cancers, including breast, ovarian, and uterine cancers (10, 11, 14, 15). Uterine fibroids, which have been associated with an increased prevalence of thyroid nodules (16, 17), proliferate in the presence of estradiol and progesterone (18, 19). In addition to benign breast disease and endometriosis being possible disease precursors (14, 15), benign breast and gynecological conditions could be considered as potential indicators of lifetime sex steroid hormone exposure in epidemiological studies.…”

Section: Introductionmentioning

confidence: 99%

Benign Breast and Gynecologic Conditions, Reproductive and Hormonal Factors, and Risk of Thyroid Cancer

Braganza

González

Schonfeld

et al. 2014

Cancer Prevention Research

View full text Add to dashboard Cite

The higher incidence of thyroid cancer in women compared to men suggests an influence of sex steroid hormones in the etiology of this malignancy. We investigated a comprehensive set of potential indicators of lifetime sex steroid hormone exposure in relation to thyroid cancer risk. Using data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which enrolled 70,047 women, 50–78 years old, we prospectively examined associations of self-reported history of benign breast and gynecological conditions, reproductive factors, and exogenous sex hormone use with thyroid cancer risk. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated in models using age as the time metric. During follow-up (median=11 years), 127 women were diagnosed with first primary thyroid cancer. Older age at natural menopause (≥55 vs. <50 years: HR=2.24, 95% CI:1.20–4.18), greater estimated lifetime number of ovulatory cycles (≥490 vs. <415 cycles: HR= 2.40, 95% CI:1.33–4.30), greater number of live births (≥5 vs. 1–2: HR=1.72, 95% CI:1.05–2.82), and history of uterine fibroids (HR=1.72, 95% CI:1.18–2.50) were associated with an increased risk of thyroid cancer. Earlier age at menarche, greater number of reproductive years, history of a tubal ligation, and history of ovarian cysts were non-significantly associated with increased thyroid cancer risk. No associations were observed for oral contraceptive use, menopausal hormone therapy, or history of benign breast disease or endometriosis. In general, we found that factors reflecting a greater length of exposure to endogenous hormones, particularly during the reproductive years, were associated with risk of postmenopausal thyroid cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

Benign Breast and Gynecologic Conditions, Reproductive and Hormonal Factors, and Risk of Thyroid Cancer

Braganza

González

Schonfeld

et al. 2014

Cancer Prevention Research

View full text Add to dashboard Cite

show abstract

“…In Australia and globally, the commonest reason for hysterectomy is fibroids (Treloar et al 1999, Rice et al 2012. In the USA, uterine fibroids pose a significant cost to society, with annual direct and indirect healthcare costs estimated at up to US$34.4 billion (Cardozo et al 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Uterine fibroids are benign tumours of the myometrium and are a prevalent gynaecological condition in reproductive-aged women (reviewed by Rice et al (2012)). In Australia and globally, the commonest reason for hysterectomy is fibroids (Treloar et al 1999, Rice et al 2012.…”

Section: Introductionmentioning

confidence: 99%

Common fibroid-associated genes are differentially expressed in phenotypically dissimilar cell populations isolated from within human fibroids and myometrium

Holdsworth-Carson¹,

Zaitseva²,

Girling³

et al. 2014

Reproduction

View full text Add to dashboard Cite

Uterine fibroids are a prevalent gynaecological condition in reproductive-aged women and are the commonest reason for hysterectomy. The cellular composition of clonal fibroids are heterogeneous, with phenotypically dissimilar cells that include smooth muscle cells (SMC), vascular SMC (VSMC) and fibroblasts. The aim of our study was to investigate genes that are commonly differentially expressed between fibroid and myometrial whole tissues in phenotypically different sub-populations of cells isolated from fibroid and myometrium. Genes to be investigated by fluorescence-activated cell sorting, quantitative real-time PCR and immunocytochemistry include transforming growth factor b (TGFB) and retinoic acid (RA) signalling families and steroid hormone receptors. We hypothesised that each cell population isolated from fibroid and myometrium would differ in the expression of fibroid-associated genes. We demonstrated that phenotypically different cellular constituents of uterine fibroids differentially express cellular RA-binding protein 2 (CRABP2), progesterone receptor B (PRB) and TGFB receptor 2 mRNA in fibroid-derived cells of VSMC and SMC phenotype. CRABP2 mRNA was also differentially expressed in fibroblasts and VSMC sub-populations from within clonal fibroid tumours. We conclude that differential regulation of RA, TGFB and PR pathway transcription occurs in fibroid-associated SMC and -fibroblasts and that investigation of paracrine interactions between different cell types within the fibroid microenvironment provides an important new paradigm for understanding the pathophysiology of this common disease.

show abstract

“…Leiomyomas can cause a variety of health complications and are the leading indication for hysterectomy (1). The clinical and scientific community widely regards leiomyomas as a single entity, although substantial evidence of heterogeneity exists at several different levels, including symptoms, histopathology, therapeutic requirements, and genetic changes (2).…”

mentioning

confidence: 99%

Integrated data analysis reveals uterine leiomyoma subtypes with distinct driver pathways and biomarkers

Mehine

Kaasinen

Heinonen

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

190

231

View full text Add to dashboard Cite

Uterine leiomyomas are common benign smooth muscle tumors that impose a major burden on women's health. Recent sequencing studies have revealed recurrent and mutually exclusive mutations in leiomyomas, suggesting the involvement of molecularly distinct pathways. In this study, we explored transcriptional differences among leiomyomas harboring different genetic drivers, including high mobility group AT-hook 2 (HMGA2) rearrangements, mediator complex subunit 12 (MED12) mutations, biallelic inactivation of fumarate hydratase (FH), and collagen, type IV, alpha 5 and collagen, type IV, alpha 6 (COL4A5-COL4A6) deletions. We also explored the transcriptional consequences of 7q22, 22q, and 1p deletions, aiming to identify possible target genes. We investigated 94 leiomyomas and 60 corresponding myometrial tissues using exon arrays, whole genome sequencing, and SNP arrays. This integrative approach revealed subtype-specific expression changes in key driver pathways, including Wnt/β-catenin, Prolactin, and insulin-like growth factor (IGF)1 signaling. Leiomyomas with HMGA2 aberrations displayed highly significant up-regulation of the proto-oncogene pleomorphic adenoma gene 1 (PLAG1), suggesting that HMGA2 promotes tumorigenesis through PLAG1 activation. This was supported by the identification of genetic PLAG1 alterations resulting in expression signatures as seen in leiomyomas with HMGA2 aberrations. RAD51 paralog B (RAD51B), the preferential translocation partner of HMGA2, was up-regulated in MED12 mutant lesions, suggesting a role for this gene in the genesis of leiomyomas. FH-deficient leiomyomas were uniquely characterized by activation of nuclear factor erythroid 2-related factor 2 (NRF2) target genes, supporting the hypothesis that accumulation of fumarate leads to activation of the oncogenic transcription factor NRF2. This study emphasizes the need for molecular stratification in leiomyoma research and possibly in clinical practice as well. Further research is needed to determine whether the candidate biomarkers presented herein can provide guidance for managing the millions of patients affected by these lesions.uterine leiomyoma | transcriptional profiling | MED12 | HMGA2

show abstract

Etiology, Diagnosis, and Management of Uterine Leiomyomas

Cited by 31 publications

References 46 publications

Benign Breast and Gynecologic Conditions, Reproductive and Hormonal Factors, and Risk of Thyroid Cancer

Benign Breast and Gynecologic Conditions, Reproductive and Hormonal Factors, and Risk of Thyroid Cancer

Common fibroid-associated genes are differentially expressed in phenotypically dissimilar cell populations isolated from within human fibroids and myometrium

Integrated data analysis reveals uterine leiomyoma subtypes with distinct driver pathways and biomarkers

Contact Info

Product

Resources

About