scholarly journals Performance of the MasSpec Pen for Rapid Diagnosis of Ovarian Cancer

2019 ◽  
Vol 65 (5) ◽  
pp. 674-683 ◽  
Author(s):  
Marta Sans ◽  
Jialing Zhang ◽  
John Q Lin ◽  
Clara L Feider ◽  
Noah Giese ◽  
...  
Keyword(s):  
Machine Learning ◽  
Ovarian Cancer ◽  
Fallopian Tube ◽  
Mass Spectrometer ◽  
Cancer Diagnosis ◽  
Ion Trap ◽  
Serous Carcinoma ◽  
High Grade ◽  
Clinical Sensitivity ◽  
Tissue Diagnosis

Abstract BACKGROUND Accurate tissue diagnosis during ovarian cancer surgery is critical to maximize cancer excision and define treatment options. Yet, current methods for intraoperative tissue evaluation can be time intensive and subjective. We have developed a handheld and biocompatible device coupled to a mass spectrometer, the MasSpec Pen, which uses a discrete water droplet for molecular extraction and rapid tissue diagnosis. Here we evaluated the performance of this technology for ovarian cancer diagnosis across different sample sets, tissue types, and mass spectrometry systems. METHODS MasSpec Pen analyses were performed on 192 ovarian, fallopian tube, and peritoneum tissue samples. Samples were evaluated by expert pathologists to confirm diagnosis. Performance using an Orbitrap and a linear ion trap mass spectrometer was tested. Statistical models were generated using machine learning and evaluated using validation and test sets. RESULTS High performance for high-grade serous carcinoma (n = 131; clinical sensitivity, 96.7%; specificity, 95.7%) and overall cancer (n = 138; clinical sensitivity, 94.0%; specificity, 94.4%) diagnoses was achieved using Orbitrap data. Variations in the mass spectra from normal tissue, low-grade, and high-grade serous ovarian cancers were observed. Discrimination between cancer and fallopian tube or peritoneum tissues was also achieved with accuracies of 92.6% and 87.9%, respectively, and 100% clinical specificity for both. Using ion trap data, excellent results for high-grade serous cancer vs normal ovarian differentiation (n = 40; clinical sensitivity, 100%; specificity, 100%) were obtained. CONCLUSIONS The MasSpec Pen, together with machine learning, provides robust molecular models for ovarian serous cancer prediction and thus has potential for clinical use for rapid and accurate ovarian cancer diagnosis.

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.

scholarly journals A genetically engineered ovarian cancer mouse model based on fallopian tube transformation mimics human high-grade serous carcinoma development

2014 ◽  
Vol 233 (3) ◽  
pp. 228-237 ◽  
Author(s):  
Cheryl A Sherman-Baust ◽  
Elisabetta Kuhn ◽  
Blanca L Valle ◽  
Ie-Ming Shih ◽  
Robert J Kurman ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mouse Model ◽  
Fallopian Tube ◽  
Genetically Engineered ◽  
Serous Carcinoma ◽  
High Grade ◽  
Model Based

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.

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 Targeting progesterone signaling prevents metastatic ovarian cancer

2020 ◽  
Vol 117 (50) ◽  
pp. 31993-32004
Author(s):  
Olga Kim ◽  
Eun Young Park ◽  
Sun Young Kwon ◽  
Sojin Shin ◽  
Robert E. Emerson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Deleterious Mutation ◽  
Peritoneal Metastases ◽  
Cancer Development ◽  
Serous Carcinoma ◽  
Cancer Type ◽  
High Grade ◽  
Primary Tumors ◽  
High Risk Populations ◽  
Genetic Deletion

Effective cancer prevention requires the discovery and intervention of a factor critical to cancer development. Here we show that ovarian progesterone is a crucial endogenous factor inducing the development of primary tumors progressing to metastatic ovarian cancer in a mouse model of high-grade serous carcinoma (HGSC), the most common and deadliest ovarian cancer type. Blocking progesterone signaling by the pharmacologic inhibitor mifepristone or by genetic deletion of the progesterone receptor (PR) effectively suppressed HGSC development and its peritoneal metastases. Strikingly, mifepristone treatment profoundly improved mouse survival (∼18 human years). Hence, targeting progesterone/PR signaling could offer an effective chemopreventive strategy, particularly in high-risk populations of women carrying a deleterious mutation in the BRCA gene.

scholarly journals Tumour Versus Germline BRCA Testing in Ovarian Cancer: A Single-Site Institution Experience in the United Kingdom

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 547
Author(s):  
Iolia Akaev ◽  
Siavash Rahimi ◽  
Olubukola Onifade ◽  
Francis John Edward Gardner ◽  
David Castells-Rufas ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Unknown Origin ◽  
Parp Inhibitors ◽  
Serous Carcinoma ◽  
High Grade ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Epithelial Cancers ◽  
Pathogenic Variants ◽  
Pathogenic Mutations

The aim of this audit was to evaluate the usefulness and serviceability of testing for pathogenic mutations in BRCA1 or BRCA2 (BRCA1/2) genes in ovarian cancer (OC) patients. One hundred and thirty-five patients with more common histological sub-types of OC were retrospectively identified between 2011 and 2019. The fail rate of the molecular analysis was 7.4% (10/135). One hundred and twenty-five records were evaluated: 99 (79.2%) patients had wild-type BRCA (both somatic and germline); tumour BRCA1/2 (tBRCA1/2) pathogenic mutations were found in 20 (16%) patients with distribution between BRCA1 and BRCA2 being 40% and 60%, respectively; 13 (10.4%) patients with pathogenic variants had germline mutations; and tBRCA1/2 with variant of unknown significance (VUS), in the absence of pathogenic BRCA1 or BRCA2 variants, was detected in 6 (4.8%) patients. Our data show that expanding the molecular service to the routine first-tumour testing for patients with OC will potentially increase the detection rate of BRCA mutations, thereby providing early benefits of PARP inhibitors therapy. The tumour testing service should continue to be offered to newly diagnosed patients with high-grade epithelial cancers, including high-grade serous carcinoma, but also with carcinosarcomas and poorly-differentiated metastatic adenocarcinomas of unknown origin.

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