Molecular pathological approach of uterine intravenous leiomyomatosis.
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ABSTRACT:
SUBMITTER: Hayashi T
PROVIDER: S-EPMC9358516 | biostudies-literature | 2022 Jul
REPOSITORIES: biostudies-literature
Publications
Molecular pathological approach of uterine intravenous leiomyomatosis.
Hayashi Takuma T Yaegashi Nobuo N Konishi Ikuo I
Annals of translational medicine 20220701 13
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Project description:Intravenous leiomyomatosis (IVL) is a histologically well differentiated smooth muscle tumor with aggressive behavior, capable of extending throughout the venous system. Understanding how IVL occurs and develops is really important for diagnosing and treating it. Unfortunately, because IVL is quite rare, there aren't many comprehensive studies available. In our research, we carried out an extensive multi-omics study, gathering tissue samples from IVL cases, uterine fibroid, and normal myometrium. The single-cell RNA sequencing analysis revealed a notable difference in cell composition between IVL and uterine fibroid. Additionally, H&E staining demonstrated more frequent hydropic changes and hyalinization in IVL tissues, along with a reduced vascular density compared to both normal myometrium and uterine fibroid. In our proteomics analysis of eight paired samples of IVL and normal myometrium fresh frozen tissue, we identified proteins that were differentially expressed, mainly related to focal adhesions and regulation of the actin cytoskeleton. The most frequently involved chromosomes included deletions in 10q22.2, 10q24.32, 13q14, and 13q21-31. Correlation analyses highlighted chromosome 10q as the most frequent cytoband, with corresponding proteins involved in regulating focal adhesions and the cytoskeleton. Integrated analysis between pathological and clinical characteristics indicated that chromosome 10q deletion and vascular morphology in IVL could serve as important markers predicting aggressive behavior. Our study sheds light on the pathological and molecular changes linked to IVL, which could pave the way for new treatment approaches.
| S-EPMC11863679 | biostudies-literature
Project description:The purpose of this study was to explore the potential relationship between intravenous leiomyomatosis (IVL) and uterine myoma (UM) at the molecular level. RNA-sequencing was performed on IVL tumours, UM tumours, and adjacent normal uterine muscle. We compared the gene expression levels between IVL and normal uterine muscle, UM and normal uterine muscle, to identify differentially expressed genes (DEGs). Then we used Gene Ontology Enrichment Analysis to determine the functions of the DEGs and performed specimen cluster analysis. We obtained 98 DEGs between IVL and adjacent normal uterine muscle, and 61 DEGs between UM and adjacent normal uterine muscle. Functional enrichment of both IVL and UM DEGs showed that they are associated with hormone stimulus, extracellular matrix, and cell adhesion. Unsupervised clustering analysis showed that IVL and UM could not be separated completely. Among these dysregulated genes, we found that HOXA13 showed a distinct dysregulated status between IVL and UM. HOXA13 may therefore serves as a biomarker to distinguish IVL and UM. Our results showed that IVL and UM may have similar dysregulated gene networks. They may be closely related, and HOXA13 may serves as a biomarker to distinguish between IVL and UM.
| S-EPMC6363745 | biostudies-literature
Project description:Intravenous leiomyomatosis (IVL) is an unusual uterine smooth muscle proliferation that can be associated with aggressive clinical behavior despite a histologically benign appearance. It has some overlapping molecular characteristics with both uterine leiomyoma and leiomyosarcoma based on limited genetic data. In this study, we assessed the clinical and morphological characteristics of 28 IVL and their correlation with molecular features and protein expression, using array comparative genomic hybridization (aCGH) and Cyclin D1, p16, phosphorylated-Rb, SMARCB1, SOX10, CAIX, SDHB and FH immunohistochemistry. The most common morphologies were cellular (n = 15), usual (n = 11), and vascular (n = 5; including 3 cellular IVL showing both vascular and cellular features). Among the immunohistochemical findings, the most striking was that all IVL showed differential expression of either p16 or Cyclin D1 in comparison to surrounding nonneoplastic tissue. Cytoplasmic phosphorylated-Rb was present in all but one IVL with hyalinization. SMARCB1, FH, and SDHB were retained; S0X10 and CAIX were not expressed. The most common genetic alterations involved 1p (39%), 22q (36%), 2q (29%), 1q (25%), 13q (21%), and 14q (21%). Hierarchical clustering analysis of recurrent aberrations revealed three molecular groups: Groups 1 (29%) and 2 (18%) with associated del(22q), and Group 3 (18%) with del(10q). The remaining IVL had nonspecific or no alterations by aCGH. Genomic index scores were calculated for all cases and showed no significant difference between the 14 IVL associated with aggressive clinical behavior (extrauterine extension or recurrence) and those without (median scores 5.15 vs 3.5). Among the 5 IVL associated with recurrence, 4 had a vascular morphology and 3 had alterations of 8q. Recurrent chromosome alterations detected herein overlap with those observed in the spectrum of uterine smooth muscle tumors and involve genes implicated in mesenchymal tumors at different sites with distinct morphological features.
| S-EPMC7483566 | biostudies-literature
Project description:MethodsWe collected the clinical data of 260 patients admitted to the hospital from April 2003 to September 2019 with pathologically confirmed intravenous leiomyomatosis (IVL) and followed up with these patients regularly. Univariate and multivariate logistic regression analyses were carried out on the relevant recurrence factors.ResultsA total of 166 patients were regularly followed up, the median follow-up time was 36 (range 2-168) months, 14 (5.4%) patients eventually relapsed, and the median recurrence time was 8.5 (range 2-42) months. The univariate analysis showed that age (p = 0.003) and surgical type (p < 0.001) were associated with recurrence, and multivariate regression analysis demonstrated that surgical type was the only factor associated with recurrence (p < 0.001, OR 20.01).ConclusionsThe use of gonadotrophin releasing hormone agonist (GnRHa) cannot reduce the postsurgical recurrence rate of patients with UIVL. Compared to total hysterectomy and bilateral salpingo-oophorectomy (TH-BSO), total hysterectomy (TH) does not increase the odds of recurrence, but the chance of recurrence with tumorectomy (TE) is 20 times higher than that of TH-BSO.
| S-EPMC9293182 | biostudies-literature
Project description:Intravenous leiomyomatosis is an unusual smooth muscle neoplasm with quasi-malignant intravascular growth but a histologically banal appearance. Herein, we report expression and molecular cytogenetic analyses of a series of 12 intravenous leiomyomatosis cases to better understand the pathogenesis of intravenous leiomyomatosis. All cases were analyzed for the expression of HMGA2, MDM2, and CDK4 proteins by immunohistochemistry based on our previous finding of der(14)t(12;14)(q14.3;q24) in intravenous leiomyomatosis. Seven of 12 (58%) intravenous leiomyomatosis cases expressed HMGA2, and none expressed MDM2 or CDK4. Colocalization of hybridization signals for probes from the HMGA2 locus (12q14.3) and from 14q24 by interphase fluorescence in situ hybridization (FISH) was detected in a mean of 89.2% of nuclei in HMGA2-positive cases by immunohistochemistry, but in only 12.4% of nuclei in negative cases, indicating an association of HMGA2 expression and this chromosomal rearrangement (P=8.24 × 10(-10)). Four HMGA2-positive cases had greater than two HMGA2 hybridization signals per cell. No cases showed loss of a hybridization signal by interphase FISH for the frequently deleted region of 7q22 in uterine leiomyomata. One intravenous leiomyomatosis case analyzed by array comparative genomic hybridization revealed complex copy number variations. Finally, expression profiling was performed on three intravenous leiomyomatosis cases. Interestingly, hierarchical cluster analysis of the expression profiles revealed segregation of the intravenous leiomyomatosis cases with leiomyosarcoma rather than with myometrium, uterine leiomyoma of the usual histological type, or plexiform leiomyoma. These findings suggest that intravenous leiomyomatosis cases share some molecular cytogenetic characteristics with uterine leiomyoma, and expression profiles similar to that of leiomyosarcoma cases, further supporting their intermediate, quasi-malignant behavior.
| S-EPMC5891726 | biostudies-literature
Project description:Up to now, there are two hypothesis about the pathogenesis of the relationship of intravenous leiomyomatosis and uterine myoma. One theory suggests that the IVL comes from the smooth muscle cell in the vessel wall.The other theory indicates that the IVL derives from the uterine myometrium. However, limited to the technology, few studies have been deeply explore the underlying relation. In this study, we employ the RNA sequencing to explore the molecule relationship between IVL and uterus myoma. In order to identify the molecule relationship between IVl and uterine myoma we conducted transcriptome sequencing and bioinformaitc analysis
| EGAS00001002504 | EGA
Project description:ObjectiveUterine intravenous leiomyomatosis (IVL) is a rare and unique leiomyoma that is difficult to surgery due to its ability to extend into intra- and extra-uterine vasculature. And it is difficult to differentiate from uterine leiomyoma (LM) by conventional CT scanning, which results in a large number of missed diagnoses. This study aimed to evaluate the utility of a contrast-enhanced CT-based radiomic nomogram for preoperative differentiation of IVL and LM.Methods124 patients (37 IVL and 87 LM) were retrospectively enrolled in the study. Radiomic features were extracted from contrast-enhanced CT before surgery. Clinical, radiomic, and combined models were developed using LightGBM (Light Gradient Boosting Machine) algorithm to differentiate IVL and LM. The clinical and radiomic signatures were integrated into a nomogram. The diagnostic performance of the models was evaluated using the area under the curve (AUC) and decision curve analysis (DCA).ResultsClinical factors, such as symptoms, menopausal status, age, and selected imaging features, were found to have significant correlations with the differential diagnosis of IVL and LM. A total of 108 radiomic features were extracted from contrast-enhanced CT images and selected for analysis. 29 radiomics features were selected to establish the Rad-score. A clinical model was developed to discriminate IVL and LM (AUC=0.826). Radiomic models were used to effectively differentiate IVL and LM (AUC=0.980). This radiological nomogram combined the Rad-score with independent clinical factors showed better differentiation efficiency than the clinical model (AUC=0.985, p=0.046).ConclusionThis study provides evidence for the utility of a radiomic nomogram integrating clinical and radiomic signatures for differentiating IVL and LM with improved diagnostic accuracy. The nomogram may be useful in clinical decision-making and provide recommendations for clinical treatment.
| S-EPMC10482096 | biostudies-literature
Project description:Intravenous leiomyomatosis (IVL) is relatively rare, and the incidence of cardiac IVL is even lower. The case report introduces a 48-year-old woman with two episodes of syncope in 2021. Echocardiography showed a cord-like mass in the inferior vena cava (IVC), right atrium (RA), right ventricle (RV) and pulmonary artery. Computed tomography venography and magnetic resonance imaging showed strips in RA, RV, IVC, right common iliac vein, and internal iliac vein, as well as a round-like mass in the right uterine adnexa. Combined with the patient's prior surgical history and rare anatomical structures, surgeons used cardiovascular 3-dimensional (3D) printing technology to create patient-specific preoperative 3D printed model. The model could help surgeons to visually and accurately understand the size of IVL and its relationship to adjacent tissues. Finally, surgeons successfully performed a concurrent transabdominal resection of cardiac metastatic IVL and adnexal hysterectomy with off-cardiopulmonary bypass. Preoperative evaluation and guidance of 3D printing may play a critical role to ensure this surgery for the patient with rare anatomical structures and high surgical risk. Clinical Trial Registration: [ClinicalTrials.gov], Protocol Registration System [NCT02917980].
| S-EPMC10313392 | biostudies-literature
Project description:Multiple cutaneous and uterine leiomyomatosis is an autosomal dominant disease characterized by leiomyomas of the skin and uterus. A small proportion of patients affected by multiple cutaneous and uterine leiomyomatosis will develop renal cell carcinoma and this condition is known as hereditary leiomyomatosis and renal cell carcinoma. Diagnosis usually occurs during histological analysis of a cutaneous biopsy. Management should involve a multidisciplinary team along with periodical radiological studies to closely monitor tumor size in the uterus and kidneys. Gonadotropin-releasing hormone analogues are helpful in reducing the size of uterine fibroids.
| S-EPMC3638850 | biostudies-literature
Project description:Disseminated peritoneal leiomyomatosis (DPL) is a rare condition characterized by scattered smooth muscle nodules over the peritoneal surfaces. The pathogenesis of DPL remains unclear. Herein, we report a case of DPL occurring 7 years after laparoscopic supracervical hysterectomy with morcellation for uterine leiomyomata (UL). We analyzed both the original UL and the subsequent DPL by molecular cytogenetics to assess the role of chromosomal abnormalities in DPL pathobiology. Interestingly, all of the chromosomal aberrations detected in this case of DPL, including r(1)(p34.3q41), del(3)(q23q26.33), and t(12;14)(q14.3;q24.1), are characteristic chromosomal abnormalities detected in UL. Fluorescence in situ hybridization analysis of the initial UL confirmed an interstitial deletion spanning at least 3q24 and 3q25.1, suggesting that functional alteration of a potential gene in this chromosomal region may play a role in DPL development from UL. With the increasing rate of hysterectomy through laparoscopic approach to UL, the unique complications of laparoscopy with morcellation, especially seeding and proliferation of tumor cells over abdominal organs and peritoneum, are becoming more significant and may necessitate review of current surgical protocols to prevent future seeding of the pelvic region with tumor particles.
| S-EPMC2955189 | biostudies-literature