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  1. Primary squamous cell carcinoma of the endometrium: A rare case report
    Purbadi S, Saspriyana KY, Hellyanti T
    Med J Malaysia, 2020 09;75(5):603-605.
    PMID: 32918438
    Primary endometrial squamous cell carcinomas (PESCC) occur sporadically. It is defined as a primary carcinoma of the endometrium composed of squamous cells of varying degrees of differentiation. A 57-year-old female patient was referred to the gynaecological clinic of Faculty of Medicine, Universitas Indonesia, Dr Cipto Mangunkusumo National Referral Hospital because of abdominal enlargement with pain. Total hysterectomy and bilateral salpingectomy were performed. Histopathological examination confirmed a moderately differentiated squamous cell carcinoma, with lymph-vascular invasion. Two weeks after the operation, the patient complained of a mass on her left supraclavicular area. Fine needle aspiration biopsy revealed squamous cell carcinoma metastatic in nature. The recommended treatment was paclitaxel (175mg/m2) and carboplatin (AUC- 6), combined with pelvic radiotherapy.
    Matched MeSH terms: Endometrium/pathology*
  2. Integrated Eutopic Endometrium and Non-Depleted Serum Quantitative Proteomic Analysis Identifies Candidate Serological Markers of Endometriosis
    Manousopoulou A, Hamdan M, Fotopoulos M, Garay-Baquero DJ, Teng J, Garbis SD, et al.
    Proteomics Clin Appl, 2019 05;13(3):e1800153.
    PMID: 30488576 DOI: 10.1002/prca.201800153
    BACKGROUND: Endometriosis affects about 4% of women in the reproductive age and is associated with subfertility. The aim of the present study is to examine the integrated quantitative proteomic profile of eutopic endometrium and serum from women with endometriosis compared to controls in order to identify candidate disease-specific serological markers.

    METHODS: Eutopic endometrium and serum from patients with endometriosis (n = 8 for tissue and n = 4 for serum) are, respectively, compared to endometrium and serum from females without endometriosis (n = 8 for tissue and n = 4 for serum) using a shotgun quantitative proteomics method. All study participants are at the proliferative phase of their menstrual cycle.

    RESULTS: At the tissue and serum level, 1214 and 404 proteins are differentially expressed (DEPs) in eutopic endometrium and serum, respectively, of women with endometriosis versus controls. Gene ontology analysis shows that terms related to immune response/inflammation, cell adhesion/migration, and blood coagulation are significantly enriched in the DEPs of eutopic endometrium, as well as serum. Twenty-one DEPs have the same trend of differential expression in both matrices and can be further examined as potential disease- and tissue-specific serological markers of endometriosis.

    CONCLUSIONS: The present integrated proteomic profiling of eutopic endometrium and serum from women with endometriosis identify promising serological markers that can be further validated in larger cohorts for the minimally invasive diagnosis of endometriosis.

    Matched MeSH terms: Endometrium/pathology
  3. Fulltext Identification of NRAS Diagnostic Biomarkers and Drug Targets for Endometrial Cancer-An Integrated in Silico Approach
    Alessandro L, Low KE, Abushelaibi A, Lim SE, Cheng WH, Chang SK, et al.
    Int J Mol Sci, 2022 Nov 18;23(22).
    PMID: 36430761 DOI: 10.3390/ijms232214285
    The diagnosis of endometrial cancer involves sequential, invasive tests to assess the thickness of the endometrium by a transvaginal ultrasound scan. In 6−33% of cases, endometrial biopsy results in inadequate tissue for a conclusive pathological diagnosis and 6% of postmenopausal women with non-diagnostic specimens are later discovered to have severe endometrial lesions. Thus, identifying diagnostic biomarkers could offer a non-invasive diagnosis for community or home-based triage of symptomatic or asymptomatic women. Herein, this study identified high-risk pathogenic nsSNPs in the NRAS gene. The nsSNPs of NRAS were retrieved from the NCBI database. PROVEAN, SIFT, PolyPhen-2, SNPs&GO, PhD-SNP and PANTHER were used to predict the pathogenicity of the nsSNPs. Eleven nsSNPs were identified as “damaging”, and further stability analysis using I-Mutant 2.0 and MutPred 2 indicated eight nsSNPs to cause decreased stability (DDG scores < −0.5). Post-translational modification and protein−protein interactions (PPI) analysis showed putative phosphorylation sites. The PPI network indicated a GFR-MAPK signalling pathway with higher node degrees that were further evaluated for drug targets. The P34L, G12C and Y64D showed significantly lower binding affinity towards GTP than wild-type. Furthermore, the Kaplan−Meier bioinformatics analyses indicated that the NRAS gene deregulation affected the overall survival rate of patients with endometrial cancer, leading to prognostic significance. Findings from this could be considered novel diagnostic and therapeutic markers.
    Matched MeSH terms: Endometrium/pathology
  4. Unusual form of superficial spreading microinvasive squamous cell carcinoma of uterine cervix involving the endometrium of uterus
    Tan GC, Isa MR, Ng SP, Jamil YM
    J Obstet Gynaecol Res, 2004 Oct;30(5):363-7.
    PMID: 15327449
    Microinvasive squamous cell carcinoma of the uterine cervix is a recognized entity and is defined as carcinoma with invasion of less than 5 mm penetration of the stroma and seldom metastasized. Our patient was a 70-year-old, multiparous woman who had a microinvasive, cervical, squamous cell carcinoma. The tumor had spread superficially into the entire endometrial cavity up to the fundus, totally replacing the columnar epithelium. This is an extremely rare phenomenon, with fewer than 20 cases reported so far in the literature.
    Matched MeSH terms: Endometrium/pathology*
  5. Fulltext Apoptosis in endometria of dysfuntional uterine bleeding women
    Rekha K, Malini A, Xavier R, Baba K
    Med J Malaysia, 2005 Mar;60(1):41-5.
    PMID: 16250278
    The study of apoptosis in endometrium of women with irregular uterine bleeding and its predictive value in endometrial malignancy. Analyze apoptotic and mitotic indices and their relevance in irregular uterine bleeding. To determine the expression of Bcl-2 oncoprotein in endometrial glands from patients with irregular uterine bleeding. Department of pathology in a Government Hospital serving a varied socio-economic population in Chennai. Random samples of endometrial currettings from dysfunctional uterine bleeding (DUB) patient who underwent endometrial curettage as therapeutic and diagnostic procedure during the year 2000. Of 50 cases of endometrial samples from patients diagnosed as cases of DUB, the apoptotic and mitotic indexing was carried out and histological categorization revealed 13 cases as Anovulatory. 14 as simple hyperplasia, 5 as early secretory endometrium, 4 as mid secretory and 4 as late secretory endometrium and 7 as endometrium showing features of hormonal imbalance. Three cases were not included, due to sub-optimal processing. A good correlation of the Bcl-2 expression and the apoptotic cell morphology/indices, in the different categories of the endometria of DUB cases is observed. This preliminary study gives an insight to the existence of a correlative pattern of apoptosis in DUB cases. A prospective study on a larger number of cases may substantiate the hypothesis that the Apoptotic and Mitotic indices are useful screening methods with predictive values on development of endometrial carcinoma. It is observed that an increased apoptotic index correlating with high Bcl-2 expression, reflecting the actual cell burden. This prolonged cell survival resisting cell deletion is associated with irregular uterine bleeding endometria.
    Matched MeSH terms: Endometrium/pathology
  6. Dissemination of endometrial cells at laparoscopy and chromotubation--a preliminary report
    Kulenthran A, Jeyalakshmi N
    Int. J. Fertil., 1989 Jul-Aug;34(4):256-8.
    PMID: 2570762
    Twenty-one patients undergoing laparoscopy and chromotubation were investigated for the dissemination of endometrial cells into the pelvic cavity. Prechromotubation fluid and postchromotubation fluid from the posterior cul-de-sac were aspirated and subjected to cytological assessment. Four patients (15.4%) showed evidence of endometrial cell dissemination into the pelvic cavity.
    Matched MeSH terms: Endometrium/pathology
  7. Altered N-linked glycosylation in endometrial cancer
    Mittal P, Briggs M, Klingler-Hoffmann M, Kaur G, Packer NH, Oehler MK, et al.
    Anal Bioanal Chem, 2021 Apr;413(10):2721-2733.
    PMID: 33222001 DOI: 10.1007/s00216-020-03039-z
    It is well established that cell surface glycans play a vital role in biological processes and their altered form can lead to carcinogenesis. Mass spectrometry-based techniques have become prominent for analysing N-linked glycans, for example using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). Additionally, MALDI MS can be used to spatially map N-linked glycans directly from cancer tissue using a technique termed MALDI MS imaging (MALDI MSI). This powerful technique combines mass spectrometry and histology to visualise the spatial distribution of N-linked glycans on a single tissue section. Here, we performed N-glycan MALDI MSI on six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMA) consisting of eight EC patients with lymph node metastasis (LNM) and twenty without LNM. By doing so, several putative N-linked glycan compositions were detected that could significantly distinguish normal from cancerous endometrium. Furthermore, a complex core-fucosylated N-linked glycan was detected that could discriminate a primary tumour with and without LNM. Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS). Overall, we observed higher abundance of oligomannose glycans in tumour compared to normal regions with AUC ranging from 0.85-0.99, and lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28. A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis. In summary, N-linked glycan MALDI MSI can be used to differentiate cancerous endometrium from normal, and endometrial cancer with LNM from endometrial cancer without.
    Matched MeSH terms: Endometrium/pathology
  8. The Vabra aspirator versus the Pipelle device for outpatient endometrial sampling
    Naim NM, Mahdy ZA, Ahmad S, Razi ZR
    Aust N Z J Obstet Gynaecol, 2007 Apr;47(2):132-6.
    PMID: 17355303 DOI: 10.1111/j.1479-828X.2007.00699.x
    OBJECTIVE: To compare the effectiveness of the Vabra aspirator and the Pipelle device as an outpatient endometrial assessment tool.
    METHOD: This was a randomised, prospective trial conducted for a period of one year.
    RESULTS: A total of 147 patients were recruited, of which 71 were in the Vabra group and 76 were in the Pipelle arm. The procedure success rate in the Pipelle group was significantly higher than the Vabra arm (98.7 vs 88.7%, P=0.02). Adequate tissue yield was also significantly more in the Pipelle arm (73.3 vs 52.4%, P=0.02). Cost-benefit analysis revealed a higher average cost per patient in the Vabra group compared to the Pipelle arm.
    CONCLUSION: This study proved that the Vabra aspirator was not as effective as the Pipelle device in obtaining endometrial tissue for histological diagnosis. Despite its higher price per unit, the Pipelle device was a more cost-effective tool for outpatient endometrial assessment.
    Study site: Medical clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia.
    Matched MeSH terms: Endometrium/pathology
  9. Endometrial and endocervical secretion: the search for histochemical differentiation
    Nieuwenhuizen L, Khalil MK, Venkatesh N, Othman NH
    Anal. Quant. Cytol. Histol., 2006 Apr;28(2):87-96.
    PMID: 16637511
    To determine the ideal histochemical stain to differentiate between non-neoplastic and neoplastic endocervix and endometrium.
    Matched MeSH terms: Endometrium/pathology
  10. Fulltext The role of endovaginal ultrasonography and the value of endometrial biopsy in breast cancer patients on tamoxifen therapy
    Sivalingam N, Pathmalingam A
    Singapore Med J, 1999 Jun;40(6):402-4.
    PMID: 10489508
    Endometrial changes have been observed when tamoxifen is used as an adjuvant therapy for carcinoma of the breast in postmenopausal women with positive estrogen receptors status.
    Matched MeSH terms: Endometrium/pathology
  11. Concordance between hysteroscopic impression and endometrial histopathological diagnosis
    Gan DE, Jawan RA, Moy FM
    Prev Med, 2013;57 Suppl:S21-3.
    PMID: 23313791 DOI: 10.1016/j.ypmed.2012.12.026
    The aim of this study was to evaluate the accuracy of hysteroscopic impression for diagnosing benign and malignant endometrial pathology.
    Matched MeSH terms: Endometrium/pathology*
  12. Combinatorial effect of genistein and female sex-steroids on uterine fluid volume and secretion rate and aquaporin (AQP)-1, 2, 5, and 7 expression in the uterus in rats
    Chinigarzadeh A, Muniandy S, Salleh N
    Environ Toxicol, 2017 Mar;32(3):832-844.
    PMID: 27235753 DOI: 10.1002/tox.22283
    We hypothesized that genistein can interfere with the regulation of uterine fluid volume, secretion rate and expression of aquaporin in the uterus by female sex-steroids, i.e., estrogen and progesterone. Therefore, the aims of this study were to investigate changes in these parameters in the presence of genistein and female sex-steroids.

    METHODS: Female Sprague-Dawley rats were ovariectomized and received 3-days estradiol-17β benzoate (E2) plus genistein (25, 50, or 100 mg kg(-1)  day(-1) ) or 3-days E2 followed by 3-days E2 plus progesterone with genistein (25, 50, or 100 mg kg(-1)  day(-1) ). A day after last treatment, uterine fluid secretion rate was determined by in vivo uterine perfusion with rats under anesthesia. Animals were sacrificed and uteri were harvested and subjected for histological analyses. Luminal/outer uterine circumference was determined and distribution of AQP-1, 2, 5, and 7 in endometrium was visualized by immunofluorescence. Expression of AQP-1, 2, 5, and 7 proteins and mRNAs were determined by Western blotting and Real-time PCR respectively.

    RESULTS: Combined treatment of E2 with high dose genistein (50 and 100 mg kg(-1)  day(-1) ) resulted in significant decrease in uterine fluid volume, secretion rate and expression of AQP-1, 2, 5, and 7 proteins and mRNAs in uterus (p 

    Matched MeSH terms: Endometrium/pathology
  13. Fulltext Cancer-associated fibroblasts promote proliferation of endometrial cancer cells
    Subramaniam KS, Tham ST, Mohamed Z, Woo YL, Mat Adenan NA, Chung I
    PLoS One, 2013;8(7):e68923.
    PMID: 23922669 DOI: 10.1371/journal.pone.0068923
    Endometrial cancer is the most commonly diagnosed gynecologic malignancy worldwide; yet the tumor microenvironment, especially the fibroblast cells surrounding the cancer cells, is poorly understood. We established four primary cultures of fibroblasts from human endometrial cancer tissues (cancer-associated fibroblasts, CAFs) using antibody-conjugated magnetic bead isolation. These relatively homogenous fibroblast cultures expressed fibroblast markers (CD90, vimentin and alpha-smooth muscle actin) and hormonal (estrogen and progesterone) receptors. Conditioned media collected from CAFs induced a dose-dependent proliferation of both primary cultures and cell lines of endometrial cancer in vitro (175%) when compared to non-treated cells, in contrast to those from normal endometrial fibroblast cell line (51%) (P<0.0001). These effects were not observed in fibroblast culture derived from benign endometrial hyperplasia tissues, indicating the specificity of CAFs in affecting endometrial cancer cell proliferation. To determine the mechanism underlying the differential fibroblast effects, we compared the activation of PI3K/Akt and MAPK/Erk pathways in endometrial cancer cells following treatment with normal fibroblasts- and CAFs-conditioned media. Western blot analysis showed that the expression of both phosphorylated forms of Akt and Erk were significantly down-regulated in normal fibroblasts-treated cells, but were up-regulated/maintained in CAFs-treated cells. Treatment with specific inhibitors LY294002 and U0126 reversed the CAFs-mediated cell proliferation (P<0.0001), suggesting for a role of these pathways in modulating endometrial cancer cell proliferation. Rapamycin, which targets a downstream molecule in PI3K pathway (mTOR), also suppressed CAFs-induced cell proliferation by inducing apoptosis. Cytokine profiling analysis revealed that CAFs secrete higher levels of macrophage chemoattractant protein (MCP)-1, interleukin (IL)-6, IL-8, RANTES and vascular endothelial growth factor (VEGF) than normal fibroblasts. Our data suggests that in contrast to normal fibroblasts, CAFs may exhibit a pro-tumorigenic effect in the progression of endometrial cancer, and PI3K/Akt and MAPK/Erk signaling may represent critical regulators in how endometrial cancer cells respond to their microenvironment.
    Matched MeSH terms: Endometrium/pathology
  14. The effect of Metformin on endometrial tumor-regulatory genes and systemic metabolic parameters in polycystic ovarian syndrome--a proof-of-concept study
    Shafiee MN, Malik DA, Yunos RI, Atiomo W, Omar MH, Ghani NA, et al.
    Gynecol Endocrinol, 2015 Apr;31(4):286-90.
    PMID: 25495168 DOI: 10.3109/09513590.2014.989982
    The aim of this proof-of-concept study was to determine the effects of three-month Metformin therapy on the expression of tumor-regulatory genes (p53, cyclin D2 and BCL-2) in the endometrium of women with polycystic ovary syndrome (PCOS). A total of 40 women, aged between 21 and 45 years with PCOS (Rotterdam criteria) were recruited. The participants were assessed at pre- and 3-month-post-Metformin therapy for the menstrual regularities, weight reduction, Ferriman Galway scores, fasting blood glucose (FBG), total cholesterol, LDL, HDL and p53, BCL-2 and cyclin D2 gene expression. Five participants conceived spontaneously after the initial recruitment. Majority (68%) resumed regular menstrual cycles after Metformin. There were significant reduction in BMI (p = 0.001), weight (p = 0.001) and Ferriman Galway scores (p = 0.001). A significant improvement was seen in mean FBG (p = 0.002), total cholesterol (p = 0.001), LDL (p = 0.003) and HDL cholesterol levels (p = 0.015). Tumor suppressor gene (p53) was significantly up-regulated after Metformin (10 out of 14 women), with p value 0.016. BCL-2 and cyclin D2 (oncogenes) were slightly up-regulated without significant difference (p = 0.119 and 0.155, respectively). In conclusion, Metformin therapy improved clinical and metabolic parameters in women with PCOS and up-regulated p53 tumor suppressor gene significantly. Further studies are however required to independently validate our findings.
    Matched MeSH terms: Endometrium/pathology
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