Anne Kathrin Höhn, Sabine Klagges, Albrecht Gläser, Sabine Taubenheim, Nadja Dornhöfer, Jens Einenkel, Grit Gesine Ruth Hiller, Christine E Brambs, Lars-Christian Horn
PURPOSE: Accurate disease classification is fundamental for the selection of the treatment approach, prognostication, selection of clinical trials and for research purposes in routine clinical practice. Extrauterine high-grade serous carcinoma (HG-SC) may arise from the ovary, the fallopian tube and rarely from the peritoneal surface epithelium. Regardless of its origin, the vast majority of patients with HG-SC share clinical symptoms, present with advanced stage disease and suffer from a poor prognosis...
September 11, 2020: Journal of Cancer Research and Clinical Oncology
John J Wallbillich, Robert T Morris, Rouba Ali-Fehmi
OBJECTIVE: To compare the frequencies of somatic homologous recombination (HR) gene mutations identified in next-generation sequencing (NGS) genomic profiling of uterine serous carcinomas (USCs) and high-grade serous ovarian carcinomas (HGSOCs). METHODS: Data for this analysis was obtained from AACR Project GENIE, a multi-institutional dataset of clinical-grade NGS genomic profiling results for many cancer sites and histologic subtypes, through cBioPortal. Patient/specimen groups used for analysis were USC and HGSOC...
September 5, 2020: Gynecologic Oncology
Wen Hu, Li Zhang, Sammy Ferri-Borgogno, Suet-Ying Kwan, Kelsey E Lewis, Han T Cun, Tsz-Lun Yeung, Pamela T Soliman, Rohinton S Tarapore, Joshua E Allen, Xinyuan Guan, Karen H Lu, Samuel C Mok, Chi-Lam Au-Yeung
Uterine serous cancer (USC) is an aggressive subtype of endometrial cancer, with poor survival and high recurrence rates. The development of novel and effective therapies specific to USC would aid in its management. However, few studies have focused solely on this rare subtype. The current study demonstrated that the orally bioavailable, investigational new drug and novel imipridone ONC206 suppressed USC cell proliferation and induced apoptosis both in vitro and in vivo. Disruption of the DRD2-mediated p38MAPK/ERK/PGC-1α network by ONC206 led to metabolic reprogramming and suppression of both glycolysis and oxidative phosphorylation...
August 27, 2020: Cancers
Giuseppe Angelico, Angela Santoro, Patrizia Straccia, Frediano Inzani, Federica Cianfrini, Saveria Spadola, Damiano Arciuolo, Michele Valente, Nicoletta D'Alessandris, Antonino Mulè, Gian Franco Zannoni
Background : The diagnostic role of Wilms' tumor 1 (WT1) is well known in gynaeco-pathological setting, since it is considered a specific marker of serous histotype and adnexal origin. Moreover, its oncogenic role has been recently highlighted in many cancers and it has also been regarded as a promising target antigen for cancer immunotherapy. However, the relationship between its expression and prognostic role in uterine cancer remains unclear. We analyzed the diagnostic and prognostic role of WT1 expression in patients with uterine carcinoma by completing a search using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and the PICOS (Participants, Intervention, Comparison, Outcomes, Study Design) model through PubMed, Scopus and Web of Science databases to identify studies that fit our search criteria...
August 26, 2020: Diagnostics
Parker Bussies, Ayi Eta, Andre Pinto, Sophia George, Matthew Schlumbrecht
Thrombocytosis (platelets ≥ 400K) is a common hematologic finding in gynecologic malignancies and associated with worse outcomes. Limited data exist on the prognostic capability of thrombocytosis in women with high-grade endometrial cancer (EC). Our objective was to describe the associations between elevated platelets at diagnosis, clinicopathologic features, and survival outcomes among women with high-grade, non-endometrioid EC. A review of the institutional cancer registry was performed to identify these women treated between 2005 and 2017...
August 22, 2020: Cancers
Jvan Casarin, Giorgio Bogani, Elisa Piovano, Francesca Falcone, Federico Ferrari, Franco Odicino, Andrea Puppo, Ferdinando Bonfiglio, Nicoletta Donadello, Ciro Pinelli, Antonio Simone Laganà, Antonino Ditto, Mario Malzoni, Stefano Greggi, Francesco Raspagliesi, Fabio Ghezzi
OBJECTIVE: Uterine serous carcinoma (USC) is a rare highly aggressive disease. In the present study, we aimed to investigate the survival implication of the systematic lymphadenectomy in patients who underwent surgery for apparent early-stage USC. METHODS: Consecutive patients with apparent early-stage USC surgically treated at six Italian referral cancer centers were analyzed. A comparison was made between patients who underwent retroperitoneal staging including at least pelvic lymphadenectomy "LND" vs...
September 2020: Journal of Gynecologic Oncology
Akiko Sugiyama, Tsuyoshi Ohta, Miyuki Obata, Kanako Takahashi, Manabu Seino, Satoru Nagase
Glutathione (GSH) is a primary antioxidant that protects cells against reactive oxygen species (ROS), and high levels of GSH promote cancer cell survival and resistance to chemotherapy. The glutamine transporter xCT is essential for the intracellular synthesis of GSH, whereby xCT determines the intracellular redox balance. However, whether xCT inhibition can overcome GSH-mediated resistance to chemotherapeutic agents in uterine serous carcinoma (USC) remains unclear. Thus, the present study investigated the effect of the xCT inhibitor, sulfasalazine (SAS) on cytotoxicity in paclitaxel-sensitive and -resistant USC cell lines...
September 2020: Oncology Letters
Roxana Cleopatra Penciu, Iulia Postolache, Liliana Steriu, Silvia Izvoranu, Andrei Adrian Tica, Iulia Diana Mocanu, Vasile Sârbu, Mariana Deacu, Irina Tica, Gabriela Izabela Bălţătescu, Oana Sorina Tica, Vlad Iustin Tica
Endometriosis (EMs) is a benign disease characterized by the presence of endometrial tissue outside the uterine cavity. EMs associated with ovarian cancer (OC) has a relative low incidence (5% to 10%), sometimes with evidence of a transition stage through atypical EMs (1.6% cases). We have assessed 135 consecutive patients with either EMs or OC and, out of them, our study reports on four cases of ovarian EMs and OC: two cases with endometrioid OC and two cases with high-grade serous OC (HGSOC). Cases with EMs and HGSOC are extremely rarely reported in the literature - we could find not more than 30 cases...
2020: Romanian Journal of Morphology and Embryology
Javier García-Sánchez, María D Torregrosa, Omar Cauli
BACKGROUND AND OBJECTIVE: Pharmacological therapy targeting the HER2 protein is one of the major breakthroughs in the treatment of cancer patients overexpressing HER2 who have increased survival rates. Despite improved survival, it is important to determine the less frequent adverse effects in order to tailor treatments more personalized to the patients' features. The possible impact of cancer treatments on cognitive functions is huge, and the effects of anti-HER 2 therapies on this issue have not been reviewed and are the objective of this study...
July 29, 2020: Endocrine, Metabolic & Immune Disorders Drug Targets
Dimitrios Nasioudis, Allison Grace Roy, Emily M Ko, Lori Cory, Robert L Giuntoli Ii, Ashley F Haggerty, Sarah H Kim, Mark A Morgan, Nawar A Latif
OBJECTIVES: The role of adjuvant treatment for early-stage uterine serous carcinoma is not defined. The goal of this study was to investigate the impact of adjuvant treatment on survival of patients with tumors confined to the endometrium. METHODS: Patients diagnosed with stage I uterine serous carcinoma with no myometrial invasion between January 2004 and December 2015 who underwent hysterectomy with at least 10 lymph nodes removed were identified from the National Cancer Database...
July 15, 2020: International Journal of Gynecological Cancer
Amanda N Fader, Dana M Roque, Eric Siegel, Natalia Buza, Pei Hui, Osama Abdelghany, Setsuko Chambers, Angeles Alvarez Secord, Laura Havrilesky, David M O'Malley, Floor J Backes, Nicole Nevadunsky, Babak Edraki, Dirk Pikaart, William Lowery, Karim ElSahwi, Paul Celano, Stefania Bellone, Masoud Azodi, Babak Litkouhi, Elena Ratner, Dan-Arin Silasi, Peter E Schwartz, Alessandro D Santin
PURPOSE: Uterine-serous-carcinoma (USC) is an aggressive variant of endometrial cancer. On the basis of preliminary results of a multicenter, randomized phase II trial, trastuzumab (T), a humanized-mAb targeting Her2/Neu, in combination with carboplatin/paclitaxel (C/P), is recognized as an alternative in treating advanced/recurrent HER2/Neu-positive USC. We report the updated survival analysis of NCT01367002. PATIENTS AND METHODS: Eligible patients had stage III to IV or recurrent disease...
June 29, 2020: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Shitong Lin, Yifan Meng, Canhui Cao, Ping Wu, Peipei Gao, Wenhua Zhi, Ting Peng, Peng Wu
Background: We aimed to identify differentially expressed pseudogenes and explore their potential functions in four types of common gynecological malignancies (e.g., cervical squamous cell carcinoma, ovarian serous cystadenocarcinoma, uterine corpus endometrial carcinoma, and uterine carcinosarcoma) using bioinformatics technology. Materials and methods: We identified up-regulated and down-regulated pseudogenes and built a pseudogene-miRNA-mRNA regulatory network through public datasets to explore their potential functions in carcinogenesis and cancer prognosis...
2020: Cancer Cell International
Olga T Filippova, Mario M Leitao
INTRODUCTION: Uterine cancer is the most common gynecologic malignancy, although fortunately, 75% of women present with early-stage disease. A major area of controversy regarding the management of the disease concerns postoperative therapy for both women with early- and advanced-stage endometrial carcinoma. Here, we review landmark evidence that can help guide clinical decision-making in the treatment of women diagnosed with endometrial cancer. AREAS COVERED: In this review, we present the latest data driving decisions for both surgical management and postoperative therapy for women with endometrial carcinoma...
June 22, 2020: Expert Review of Anticancer Therapy
Laudine Communal, Mauricio Medrano, Fabrice Sircoulomb, Joshua Paterson, Martin Köbel, Kurosh Rahimi, Paul Hoskins, Dongsheng Tu, Stephanie Lheureux, Amit Oza, Laurie Ailles, Diane Provencher, Robert Rottapel, Anne-Marie Mes-Masson
High-grade serous carcinoma of uterine adnexa (HGSC) is the most frequent histotype of epithelial ovarian cancer and has a poor 5-year survival rate due to late-stage diagnosis and the poor efficacy of standard treatments. Novel biomarkers of cancer outcome are needed to identify new targetable pathways and improve personalized treatments. Cell-surface screening of 26 HGSC cell lines by high-throughput flow cytometry identified junctional adhesion molecule 1 (JAM-A, also known as F11R) as a potential biomarker...
June 8, 2020: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Willem Jan van Weelden, Louis J M van der Putten, Márcia A Inda, Anne van Brussel, Marc P L M Snijders, Lisanne M M Schriever, Johan Bulten, Leon F A G Massuger, Anja van de Stolpe, Johanna M A Pijnenborg
BACKGROUND: Oestrogen receptor (ER) expression is a prognostic biomarker in endometrial cancer (EC). However, expression does not provide information about the functional activity of the ER pathway. We evaluated a model to quantify ER pathway activity in EC, and determined the prognostic relevance of ER pathway activity. METHODS: ER pathway activity was measured in two publicly available datasets with endometrial and EC tissue, and one clinical cohort with 107 samples from proliferative and hyperplastic endometrium and endometrioid-type EC (EEC) and uterine serous cancer (USC)...
June 8, 2020: British Journal of Cancer
Ninad Oak, Andrew D Cherniack, R Jay Mashl, Fred R Hirsch, Li Ding, Rameen Beroukhim, Zeynep H Gümüş, Sharon E Plon, Kuan-Lin Huang
BACKGROUND: Distinct prevalence of inherited genetic predisposition may partially explain the difference of cancer risks across ancestries. Ancestry-specific analyses of germline genomes are required to inform cancer genetic risk and prognosis of diverse populations. METHODS: We conducted analyses using germline and somatic sequencing data generated by The Cancer Genome Atlas. Collapsing pathogenic and likely pathogenic variants to cancer predisposition genes (CPG), we analyzed the association between CPGs and cancer types within ancestral groups...
May 29, 2020: Genome Medicine
Willem Jan van Weelden, Casper Reijnen, Florine A Eggink, Dorry Boll, Petronella B Ottevanger, Hetty A van den Berg, Maaike A van der Aa, Johanna M A Pijnenborg
BACKGROUND: Patients with International Federation of Gynaecology and Obstetrics (FIGO) stage III endometrial cancer (EC) have a substantial risk of adverse outcomes. After surgery, adjuvant therapy is recommended with external beam radiotherapy (EBRT), chemotherapy (CT) or both EBRT and CT. Recent trials suggest that EBRT + CT is superior to EBRT or CT alone but also results in more toxicity. We have compared the outcome of different adjuvant treatments in a population-based cohort to identify subgroups that benefit most from EBRT + CT...
July 2020: European Journal of Cancer
Hui Li, Xiaofei Xie, Yunyun Liu, Xiaoxin Huang, Haoliang Lin, Jing Li, Zhongqiu Lin
OBJECTIVE: Evidence on uterine serous cancer (USC) prognosis has been limited and inconclusive. We aim to explore the survival benefits of comprehensive lymphadenectomy in USC patients after surgery and develop a prognostic nomogram to predict survival. METHODS: USC patients who had undergone hysterectomy between 2010 and 2015 were identified from Surveillance, Epidemiology and End Results (SEER) database. The relationship between the extent of lymphadenectomy and survival, including overall survival (OS) and cancer-specific survival (CSS), was estimated with Kaplan-Meier (K-M) analysis...
July 2020: European Journal of Surgical Oncology
M Ruhul Quddus, Katrine Hansen, Umadevi Tantravahi, C James Sung
The human epidermal growth factor receptor 2 (Her2) is tested in many human cancers, including breast, bladder, pancreatic, ovarian and stomach. The American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) have issued Clinical Practice Guidelines for reporting Her2 results for breast carcinomas (Wolf et al., 2018). For the last 1-2 years Her2/neu is tested in endometrial serous carcinoma, especially in recurrent tumors or non-responsive tumors as an option for additional treatment...
May 2020: Gynecologic Oncology Reports
Xu Feng, Ranran Tang, Runjie Zhang, Huan Wang, Zhaodong Ji, Yang Shao, Shuoer Wang, Tianying Zhong, Yun Gu, Jiao Meng
Gynaecologic and breast cancers share some similarities at the molecular level. The aims of our study are to highlight the similarities and differences about IDO1, an important immune-related gene in female cancers. The NGS data from TCGA of cervical squamous cell carcinoma (CESC), ovarian serous cystadenocarcinoma (OV), uterine corpus endometrial carcinoma (UCEC), uterine carcinosarcoma (UCS) and breast invasive carcinoma (BRCA) were analysed to identify molecular features, and clinically significant and potential therapeutic targets of IDO1...
March 30, 2020: Journal of Cellular and Molecular Medicine
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