scholarly journals Loss of tubal ciliated cells as a risk for “ovarian” or pelvic serous carcinoma

2020 ◽  
Author(s):  
Yue Wang ◽  
Wanrun Lin ◽  
Yiying Wang ◽  
Yan Wang ◽  
Setsuko Chambers ◽  
...  
Keyword(s):  
High Risk ◽  
Fallopian Tube ◽  
Low Risk ◽  
Serous Carcinoma ◽  
Secretory Cells ◽  
High Grade ◽  
Ciliated Cells ◽  
Anatomic Site ◽  
Pelvic Serous Carcinoma

Abstract Background Recent advances suggest the fallopian tube as the main anatomic site for high-grade ovarian or pelvic serous carcinoma (O/PSC). Human fallopian tube is mainly lined by two cell types, secretory and ciliated cells. Large number of studies on the biologic role of tubal secretory cells in O/PSC have been performed in the last decade. However, the role of tubal ciliated cells in relation to the development of O/PSC has rarely been explored. The purpose of this study was to determine if change of the tubal ciliated cells shows difference in age and location and to examine their association with serous neoplasia. Methods Three groups (low-risk or benign control, high-risk, and O/PSC) of patients were age matched. The age data was stratified by 10-year intervals ranging from age 20 to older than 80. Ciliated cells from both tubal fimbria and ampulla segments were counted by microscopy and by tubulin immunohistochemical staining. The data was analyzed by standard contingency table, Poisson distribution methods, nonparametric Mann–Whitney U-tests and Spearman correlation analysis after age justification. Results The study revealed that the absolute number of tubal ciliated cells decreased significantly with age within each group. A reduction in ciliated cells within the fallopian tube remained a significant risk factor for serous neoplasia after age adjustment. A dramatic decrease of tubal ciliated cells in both tubal segments was identified in patients with high-risk and with O/PSC compared to those in the low-risk (benign control) group (p < 0.001). Further, within the fimbria segment, a reduced number of tubal ciliated cells was more prevalent in the high-risk group when compared to those in O/PSC group. Conclusion Our findings suggest that reduced number of ciliated cells within the fallopian tube represents a hallmark of early serous carcinogenesis. Findings also support a relationship between loss of tubal ciliated cells and aging, the presence of high-risk factors, and co-existing ovarian or pelvic high-grade serous cancers. This represents an early study identifying the role of tubal ciliated cells in the process of high-grade O/PSC development.

scholarly journals Culprit or Bystander? The Role of the Fallopian Tube in “Ovarian” High-Grade Serous Carcinoma

2016 ◽  
Vol 6 (12) ◽  
pp. 1309-1311 ◽  
Author(s):  
Elizabeth M. Swisher ◽  
Rochelle L. Garcia ◽  
Mark R. Kilgore ◽  
Barbara M. Norquist
Keyword(s):  
Fallopian Tube ◽  
Serous Carcinoma ◽  
High Grade

scholarly journals Cell Origins of High-Grade Serous Ovarian Cancer

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 433 ◽  
Author(s):  
Jaeyeon Kim ◽  
Eun Park ◽  
Olga Kim ◽  
Jeanne Schilder ◽  
Donna Coffey ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Fallopian Tube ◽  
Malignant Tumors ◽  
Clinical Importance ◽  
Serous Carcinoma ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Clinical Behavior ◽  
High Risk Women

High-grade serous ovarian cancer, also known as high-grade serous carcinoma (HGSC), is the most common and deadliest type of ovarian cancer. HGSC appears to arise from the ovary, fallopian tube, or peritoneum. As most HGSC cases present with widespread peritoneal metastases, it is often not clear where HGSC truly originates. Traditionally, the ovarian surface epithelium (OSE) was long believed to be the origin of HGSC. Since the late 1990s, the fallopian tube epithelium has emerged as a potential primary origin of HGSC. Particularly, serous tubal intraepithelial carcinoma (STIC), a noninvasive tumor lesion formed preferentially in the distal fallopian tube epithelium, was proposed as a precursor for HGSC. It was hypothesized that STIC lesions would progress, over time, to malignant and metastatic HGSC, arising from the fallopian tube or after implanting on the ovary or peritoneum. Many clinical studies and several mouse models support the fallopian tube STIC origin of HGSC. Current evidence indicates that STIC may serve as a precursor for HGSC in high-risk women carrying germline BRCA1 or 2 mutations. Yet not all STIC lesions appear to progress to clinical HGSCs, nor would all HGSCs arise from STIC lesions, even in high-risk women. Moreover, the clinical importance of STIC remains less clear in women in the general population, in which 85–90% of all HGSCs arise. Recently, increasing attention has been brought to the possibility that many potential precursor or premalignant lesions, though composed of microscopically—and genetically—cancerous cells, do not advance to malignant tumors or lethal malignancies. Hence, rigorous causal evidence would be crucial to establish that STIC is a bona fide premalignant lesion for metastatic HGSC. While not all STICs may transform into malignant tumors, these lesions are clearly associated with increased risk for HGSC. Identification of the molecular characteristics of STICs that predict their malignant potential and clinical behavior would bolster the clinical importance of STIC. Also, as STIC lesions alone cannot account for all HGSCs, other potential cellular origins of HGSC need to be investigated. The fallopian tube stroma in mice, for instance, has been shown to be capable of giving rise to metastatic HGSC, which faithfully recapitulates the clinical behavior and molecular aspect of human HGSC. Elucidating the precise cell(s) of origin of HGSC will be critical for improving the early detection and prevention of ovarian cancer, ultimately reducing ovarian cancer mortality.

Challenging Salpingectomy as a Risk-Reducing Measure for Ovarian Cancer: Histopathological Analysis of the Tubo-Ovarian Interface in Women Undergoing Risk-Reducing Salpingo-oophorectomy

2017 ◽  
Vol 27 (4) ◽  
pp. 703-707 ◽  
Author(s):  
Chloe Ayres ◽  
Gayanie Ratnayake ◽  
Orla McNally ◽  
Michael Quinn
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Fallopian Tube ◽  
High Risk Patient ◽  
Primary Site ◽  
Serous Carcinoma ◽  
Histopathological Analysis ◽  
High Grade ◽  
Bilateral Salpingectomy ◽  
Risk Reducing

ObjectiveOpportunistic bilateral salpingectomy is now promoted for women at the time of hysterectomy for a benign disease, consequent to the fimbrial end of the fallopian tube emerging as the primary site for carcinogenesis in high-grade serous carcinomas. In high-risk women with an identified germ line mutation, bilateral salpingo-oophorectomy offers the greatest risk reduction for ovarian cancer. Currently, no prospective evidence exists with respect to the effectiveness of opportunistic salpingectomy alone in preventing ovarian cancer. Although it is thought that there is no direct connection between the ovary and its adjacent fallopian tube, we often find remnants of the fimbria adherent to the ovary at the time of surgery. If this tubo-ovarian interface is not separate, then practices such as salpingectomy and radical fimbriectomy may be incomplete, and the effectiveness of this technique as a prophylactic strategy may need reconsideration. We aimed to establish whether there might exist a direct attachment of the fimbria to the ovary by examining this interface in surgically removed specimens.MethodsThe tubes and ovaries of 20 women undergoing risk-reducing salpingo-oophorectomy were examined using the Sectioning and Extensively Examining the Fimbriated End of the Tubes protocol and p53 immunohistochemistry for lesions suspicious of serous intraepithelial tubal carcinoma.ResultsThree specimens showed fimbria adherent to the ovary at the histopathological analysis. One p53 signature was identified, but there were no occult cancers or serous intraepithelial tubal carcinomas.ConclusionsAlthough only a small study, the findings show that microscopic fimbriae are adherent to the ovary. This relationship challenges the recommendation for bilateral salpingectomy alone for risk-reducing surgery because the primary site of carcinogenesis may be left on the ovary to later develop into a high-grade serous carcinoma. A larger study is needed to assess our findings related to the tubo-ovarian interface and its implications for long-term ovarian cancer development. Until then, caution on using this technique alone in the high-risk patient should be adopted.

The Fallopian Tube: Primary Site of Most Pelvic High-grade Serous Carcinomas

2009 ◽  
Vol 19 (1) ◽  
pp. 58-64 ◽  
Author(s):  
Shannon Salvador ◽  
Blake Gilks ◽  
Martin Köbel ◽  
David Huntsman ◽  
Barry Rosen ◽  
...  
Keyword(s):  
Oral Contraceptive ◽  
Fallopian Tube ◽  
English Language ◽  
Contraceptive Use ◽  
Early Stage ◽  
Tubal Ligation ◽  
Serous Carcinoma ◽  
Screening Methods ◽  
High Grade ◽  
Pelvic Serous Carcinoma

Epithelial ovarian cancer is the most common cause of mortality from gynecologic malignancy, and most of epithelial cancers are of serous type. The site of origin of pelvic high-grade serous carcinoma has been the subject of debate for 60 years. This paper reviews the evidence that pelvic serous carcinoma originates from the fallopian tube mucosa and puts forward a theory that inflammation in the tube, caused by menstrual cytokines or infection, is critical to the genesis of these tumors. Other risk factors for pelvic serous carcinoma will be reviewed, including oral contraceptive use, parity, infertility, and tubal ligation.Studies were identified for this review by searching the English language literature in the MEDLINE database between the years 1995 and 2007 using the following keywords: fallopian tube neoplasia, ovarian serous adenocarcinoma, pregnancy, oral contraceptive, infertility, pelvic inflammatory disease, cytokines, menstruation, and tubal ligation, followed by an extensive review of bibliographies from articles found through the search.The clinical implications of this theory are discussed, and a change in surgical practice is recommended, with salpingectomy at the time of simple hysterectomy. This theory also has implications for the development of new methods of screening for pelvic serous carcinomas, as there are no screening methods that are currently available to find this form of cancer in an early stage. Inflammatory markers could be detected in the vagina from the fallopian tube indicating possible chronic inflammation and a risk factor for mutagenesis leading to serous carcinoma.

scholarly journals Primary High Grade Serous Carcinoma of the Fallopian Tube: A Case Report

2020 ◽  
Vol 58 (231) ◽  
Author(s):  
Ramesh Dhakhwa ◽  
Anshu Vaidya ◽  
Amrita Giri ◽  
Archana Shakya ◽  
Achala Vaidya
Keyword(s):  
Fallopian Tube ◽  
Lower Abdominal Pain ◽  
Abnormal Uterine Bleeding ◽  
Total Abdominal Hysterectomy ◽  
Figo Stage ◽  
Abdominal Hysterectomy ◽  
Serous Carcinoma ◽  
Ca 125 ◽  
High Grade ◽  
Anatomic Site

A 49-year-old, perimenopausal nulliparous woman with lower abdominal pain and abnormal uterine bleeding. Clinical and radiological findings suggested a right adnexal tumor. CA-125 level was moderately elevated. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was done. Peroperative findings revealed a soft to friable growth arising from right fallopian tube with no involvement of ovaries. Histopathologic examination confirmed it to be a high grade serous carcinoma, FIGO stage IA. The histomorphology resembled high grade serous carcinoma of ovary, however ovaries on both sides appeared unremarkable. Surgery was uneventful and the patient was discharged after seven days of hospital stay. She did not receive postoperative chemotherapy or radiotherapy and is under follow-up. The case is reported for its occurrence in an uncommon anatomic site and preoperative dilemma with relevant review of literature.

scholarly journals PAX8 expression in high-grade serous ovarian cancer positively regulates attachment to ECM via Integrin β3

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Amata Amy Soriano ◽  
Tiziana de Cristofaro ◽  
Tina Di Palma ◽  
Serena Dotolo ◽  
Priyanka Gokulnath ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Fallopian Tube ◽  
Critical Role ◽  
Serous Carcinoma ◽  
Secretory Cells ◽  
Ovarian Cancer Cells ◽  
High Grade ◽  
Adhesion Properties ◽  
Pax8 Expression

Abstract Background Ovarian cancer is the third most common cause of death among gynecologic malignancies worldwide. Understanding the biology and molecular pathogenesis of ovarian epithelial tumors is key to developing improved prognostic indicators and effective therapies. We aimed to determine the effects of PAX8 expression on the migrative, adhesive and survival capabilities of high-grade serous carcinoma cells. Methods PAX8 depleted Fallopian tube secretory cells and ovarian cancer cells were generated using short interfering siRNA. Anoikis resistance, cell migration and adhesion properties of PAX8 silenced cells were analyzed by means of specific assays. Chromatin immunoprecipitation (ChIP) was carried out using a PAX8 polyclonal antibody to demonstrate that PAX8 is able to bind to the 5′-flanking region of the ITGB3 gene positively regulating its expression. Results Here, we report that RNAi silencing of PAX8 sensitizes non-adherent cancer cells to anoikis and affects their tumorigenic properties. We show that PAX8 plays a critical role in migration and adhesion of both Fallopian tube secretory epithelial cells and ovarian cancer cells. Inhibition of PAX8 gene expression reduces the ability of ovarian cancer cells to migrate and adhere to the ECM and specifically to fibronectin and/or collagen substrates. Moreover, loss of PAX8 strongly reduces ITGB3 expression and consequently the correct expression of the αvβ3 heterodimer on the plasma membrane. Conclusions Our results demonstrate that PAX8 modulates the interaction of tumor cells with the extracellular matrix (ECM). Notably, we also highlight a novel pathway downstream this transcription factor. Overall, PAX8 could be a potential therapeutic target for high-grade serous carcinoma.

scholarly journals Natural Herbal Estrogen-Mimetics (Phytoestrogens) Promote the Differentiation of Fallopian Tube Epithelium into Multi-Ciliated Cells via Estrogen Receptor Beta

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 722
Author(s):  
Maobi Zhu ◽  
Sen Takeda ◽  
Tomohiko Iwano
Keyword(s):  
Estrogen Receptor ◽  
Cell Differentiation ◽  
Epithelial Cells ◽  
Fallopian Tube ◽  
Ciliated Cell ◽  
Estrogen Receptor Beta ◽  
Notch Pathway ◽  
Secretory Cells ◽  
Ciliated Cells ◽  
Receptor Beta

Phytoestrogens are herbal polyphenolic compounds that exert various estrogen-like effects in animals and can be taken in easily from a foodstuff in daily life. The fallopian tube lumen, where transportation of the oocyte occurs, is lined with secretory cells and multi-ciliated epithelial cells. Recently, we showed that estrogen induces multi-ciliogenesis in the porcine fallopian tube epithelial cells (FTECs) through the activation of the estrogen receptor beta (ERβ) pathway and simultaneous inhibition of the Notch pathway. Thus, ingested phytoestrogens may induce FTEC ciliogenesis and thereby affect the fecundity. To address this issue, we added isoflavones (genistein, daidzein, or glycitin) and coumestan (coumestrol) to primary culture FTECs under air–liquid interface conditions and assessed the effects of each compound. All phytoestrogens except glycitin induced multi-ciliated cell differentiation, which followed Notch signal downregulation. On the contrary, the differentiation of secretory cells decreased slightly. Furthermore, genistein and daidzein had a slight effect on the proportion of proliferating cells exhibited by Ki67 expression. Ciliated-cell differentiation is inhibited by the ERβ antagonist, PHTPP. Thus, this study suggests that phytoestrogens can improve the fallopian tube epithelial sheet homeostasis by facilitating the genesis of multi-ciliated cells and this effect depends on the ERβ-mediated pathway.

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