Ovarian Cancer
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Cancer of the ovaries are the second most common group of gynaecologic cancers, and account for about 5% of all women's cancers. There are two main types; (i) epithelial tumours (carcinomas) which account for 90% of ovarian cancers, and (ii) non-epithelial tumours (eg. Stroma cell and germ cell tumours of the ovary). The epithelial ovarian cancers are usually found in women aged over 40, while the non-epithelial tumours are more common in girls and young women. Epithelial ovarian cancer has few early symptoms, a risk factor is having a family history of the disease. Taking the contraceptive pill is known to be protective against ovarian cancer.

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Information for Patients and the Public
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Latest Research Publications

Information Patients and the Public (21 links)

Information for Health Professionals / Researchers (12 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Gao X, Liu Y, Deeb D, et al.
Anticancer activity of pristimerin in ovarian carcinoma cells is mediated through the inhibition of prosurvival Akt/NF-κB/mTOR signaling.
J Exp Ther Oncol. 2014; 10(4):275-83 [PubMed] Free Access to Full Article Related Publications
Pristimerin isaquinonemethidetriterpenoidthathasshown anticancer activity against some cancer types. However, the antitumor effects of pristimerin (PM) in ovarian cancer cells have not been adequately studied. The objective of the present study was to determine the anticancer activity and its mechanism of action in human ovarian carcinoma cell lines. PM strongly inhibited the proliferation of ovarian cancer cells by inducing apoptosis characterized by increased annexin V-binding, cleavage of poly (ADP-ribose) polymerase (PARP-1) and procaspases-3, -8 and -9. Furthermore, PM caused mitochondrial depolarization. Western blot analysis showed inhibition of prosurvival phospho-AKT (p-AKT), nuclear factor kappa B (NF-κB) (p65) and phospho-mammalian target of rapamycin (p-mTOR) signaling proteins in cells treated with PM. Treatment with PM also inhibited the expression of NF-κB-regulated antiapoptotic Bcl-2, Bcl-xL, c-IAP1 and survivin. Thus, our data showing potent antiproliferative and apoptosis-inducing activity of PM in ovarian carcinoma cells through the inhibition of AKT/ NF-κB/ mTOR signaling pathway warrant further investigation of PM for the management of ovarian cancer.

Related: Apoptosis Mitochondrial Mutations in Cancer AKT1 Signal Transduction MTOR

Guzel AI, Yalinkaya A, Alomeroglu M
A rare case of acute abdomen: torsionated ovarian myoma.
J Exp Ther Oncol. 2014; 10(4):255-7 [PubMed] Related Publications
Ovarian leiomyoma is a rare ovarian tumor and also rare cause of acute abdomen. A 64 year old, postmenopausal woman applied to our clinic with severe acute abdominal pain. On abdominal examination, there were abdominal tenderness, defense and rebound. On ultrasonographic examination, we detected a 6 cm of pelvic mass. Because she had acute abdomen we performed laparotomy by midline incision and excised a 6cm ovarian mass on right ovary. The mass had been reported as ovarian leiomyoma on frozen section by pathology department.

Kanda M, Sonoyama A, Ohara N
Normal-sized ovary carcinoma syndrome (NOCS) detected with FDG-PET/CT.
Eur J Gynaecol Oncol. 2014; 35(5):597-9 [PubMed] Related Publications
BACKGROUND: Normal-sized ovary carcinoma syndrome (NOCS) is an ovarian cancer with ovaries being of normal size, accompanied by diffuse metastatic disease of the peritoneal cavity.
CASE: A 39-year-old woman presented with lower abdominal pains. The computed tomopraphy (CT) of the chest, esophagogastroduodenography, and colonoscopy showed no remarkable findings. Amagnetic resonance imaging (MRI) displayed a slightly enlarged right ovary, thickening of the peritoneum, and massive ascites. The right ovary showed high intensity on T2 images and scattered low intensity spots on diffusion-weighted images. The cytology of ascites suspected adenocarcinoma cells. A positron emission tomography (PET) and CT using 18F-fluorodeoxyglucose (FDG) demonstrated markedly increased FDG uptake at the right ovary and peritoneum. The presumptive diagnosis of normal-sized ovary carcinoma syndrome was made. She underwent a total hysterectomy, bilateral salpingo-oophorectomy, pelvic lymphadenectomy, and partial omentectomy. The pathological examination revealed serous cystadenocarcinoma of the right ovary.
CONCLUSION: FDG-PET/CT is useful for the detection of NOCS.

Pestana I, Costal A, Mota R, et al.
Paraneoplastic limbic encephalitis--neurologic paraneoplastic syndrome associated with ovarian malignancy--the importance of clinical recognition.
Eur J Gynaecol Oncol. 2014; 35(5):592-4 [PubMed] Related Publications
Paraneoplastic limbic encephalitis (PLE) is a rare disorder and it is also under-reported due to the difficulty in establishing the diagnosis. The delay in treatment could potentially lead to devastating neurological outcomes. The authors report a 32-year-old Caucasian, nullipara woman, who presented with a subacute dementia associated to generalized tonic-clonic seizure with rapid progression to coma. The diagnosis of immature ovarian teratoma surgical Stage FIGO IA R0 with PLE was confirmed. The patient began earlier oral corticosterois and human intravenous immunoglobulin. She was discharged one month after surgery with no neurologic deficit and remains three years later in oncological remission. A diagnosis of PLE should be considered in the differential diagnosis of unexplained dementias. Early diagnosis, treatment of the underlying malignancy, and prompt intervention with immunotherapy in this patient at the onset of presentation facilitated regression of the neurological syndrome and explains the favorable neurological outcome.

Xin G, Du J, Xu Y
Isolated sacral metastases as the initial presentation from an endometroid ovarian carcinoma: a case report.
Eur J Gynaecol Oncol. 2014; 35(5):589-91 [PubMed] Related Publications
Bone metastases are rarely in ovarian carcainoma. It usually occurrs only when the cancer is advanced or recurrent. A case of endometrioid carcinoma in right ovary with intact capsule is reported. The isolated sacral metastasis was found as the initial presentation, and no distant metastases were reported.

Ki EY, Park JS, Mun JB, Hur SY
Primary ovarian malignant mixed mesodermal tumor: report of four cases.
Eur J Gynaecol Oncol. 2014; 35(5):584-8 [PubMed] Related Publications
Malignant mixed mesodermal tumors (MMMTs) are highly aggressive and usually diagnosed at advanced stages. MMMT originates from either the ovary or the uterus. Because this disease is relatively rare, an optimal treatment modality has not yet been established. The authors report four cases of ovarian MMMT (one heterologous MMMT and three homologous MMMTs) during 1990-2011. The patients underwent operation immediately after histopathologically confirmation and were treated with platinum-based combination chemotherapy. The extent of operation, the outcomes of radiation therapy, and the proper chemotherapeutic regimen are still controversial. The authors report herein four cases of ovarian MMMTs alone with a brief literature review.

Qiao N, Zhu Y, Li H, et al.
Expression of heat shock protein 20 inversely correlated with tumor progression in patients with ovarian cancer.
Eur J Gynaecol Oncol. 2014; 35(5):576-9 [PubMed] Related Publications
OBJECTIVE: To investigate a possible correlation between expression levels of heat shock protein 20 (HSP20) and tumor progression in patients with ovarian cancer.
MATERIALS AND METHODS: The study included 34 patients with ovarian cancer who were to undergo surgery, seven patients with ovarian carcinoid tumors, and five patients with normal ovaries as a control group. Ovarian tissues were obtained from patients by surgical resection and then analyzed by western blot.
RESULTS: Expression levels of HSP20 were inversely correlated with the grade of malignancy.
CONCLUSION: The present findings suggest that HSP20 may play a protective role against the progression of ovarian cancer. Thus, HSP20 may represent a new target for the prediction and treatment of ovarian cancer.

Tianmin X, Weiqin C, Shuying W, et al.
Protection of ovarian function during chemotherapy for ovarian cancer.
Eur J Gynaecol Oncol. 2014; 35(5):562-5 [PubMed] Related Publications
The protection of ovarian function during chemotherapy is an urgent issue to be resolved after the fertility preserving surgery on patients with ovarian cancer. The paper summarizes and analyzes the research progress on the protective measures in the aspects of gonadotropin releasing hormone analogue (GnRHa), cell protecting agents, and traditional Chinese medical science and drugs.

Jin Z, Gu J, Xin X, et al.
Expression of hexokinase 2 in epithelial ovarian tumors and its clinical significance in serous ovarian cancer.
Eur J Gynaecol Oncol. 2014; 35(5):519-24 [PubMed] Related Publications
"Warburg effect" emphasizes that malignant cells exhibit active glycolysis even under aerobic conditions. Hexokinase 2 (HK2) is a key glycolytic enzyme that helps to exhibit a "Warburg effect". In the present study, the main aim was to detect the expression of HK2 in epithelial ovarian tumor tissues. Immunohistochemistry and qRT-PCR were used to examine the expression of HK2 in different epithelial ovarian tissues. The expression of HK2 in ovarian cancer tissues was significantly higher than that in normal ovarian, benign, and borderline tumors both in protein (p < 0.001) and mRNA (p < 0.05) levels. HK2 expression was significantly higher in Stage III/IV compared to Stage III (p < 0.001). Expression of HK2 in poorly-differentiated carcinoma was higher than that in well-differentiated carcinoma (p = 0.008). The level of HK2 was higher in serous groups than in non-serous groups in both protein (p = 0.008) and mRNA (p < 0.05) level. Collectively, HK2 is highly expressed in epithelial ovarian cancer, especially in serous groups. Its expression is related with clinical stage and histological differentiation.

Baser E, Gungor T, Togrul C, et al.
Preoperative prediction of poor prognostic parameters and adjuvant treatment in women with pure endometrioid type endometrial cancer: what is the significance of tumor markers?
Eur J Gynaecol Oncol. 2014; 35(5):513-8 [PubMed] Related Publications
PURPOSE OF THE STUDY: The study was conducted to determine whether preoperative serum levels of cancer antigen (CA) 125, CA15- 3, CA19-9, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) are associated clinicopathologically with poor prognostic parameters and adjuvant treatment requirements in women with pure endometrioid endometrial cancer (EEC).
MATERIALS AND METHODS: The authors performed a retrospective review of EEC cases that were treated between January 2008 and January 2011. The association between preoperative tumor markers and prognostic parameters, recurrence risk, and adjuvant treatment requirements were investigated. Following univariate analyses, receiver-operating characteristic (ROC) curves were constructed for each marker to assess their capacity to predict prognostic parameters and need for adjuvant treatment.
RESULTS: A total of 166 EEC cases were identified. Mean CA125, CA15-3, and CA19-9 levels were higher in cases that required adjuvant treatment (p < 0.05). CA125 had significant power for prediction of extrauterine disease, tumor size > two cm, lymphovascular space invasion (LVSI), deep myometrial invasion, cervical involvement, adnexal involvement, positive cytology, lymph node metastasis, and adjuvant treatment requirement. CA15-3 was a significant marker for adjuvant treatment prediction. CA19-9 could predict deep myometrial invasion, cervical involvement, and adjuvant treatment requirement. However, CEA and AFP did not have adequate capacity to predict any of the poor prognostic parameters and adjuvant treatment requirements. CONCLUSIONs: CA125 is currently one of the most important preoperative markers for identifying EEC cases that exhibit postoperatively poor prognostic pathologic findings and a consequent need for adjuvant treatment. CA15-3 and CA19- 9 were also significant markers with limited capacity in detecting prognostic parameters.

Related: Endometrial (Uterus) Cancer Endometrial Cancer

Martins Filho A, Jammal MP, Nomelini RS, Murta EF
The immune response in malignant ovarian neoplasms.
Eur J Gynaecol Oncol. 2014; 35(5):487-91 [PubMed] Related Publications
The objective of this study was to review studies that have investigated the immune response in the presence of a malignant ovarian neoplasia. A review of the literature was performed to identify studies of malignant ovarian neoplasia, particularly studies that addressed the potential for cytokines, nitric oxide, and lymphocytes to mediate an immune response against ovarian cancer. Certain subsets of tumor-infiltrating leukocytes and/or tumor-associated leukocytes have been found to correlate with an improved disease prognosis, while other lymphocyte subsets (such as CD3+/CD4+/CD25+ T cells) have been associated with a poor prognosis. These data suggest that cytokines can have a protective role, or can promote an immune system defense against a cancer. In particular, certain cytokines (e.g., IL 8, IL 10) represent attractive candidates for the development of new diagnostic, prognostic, and therapeutic strategies for the treatment of ovarian cancer.

Related: Cytokines

Kandalaft PL, Gown AM, Isacson C
The lung-restricted marker napsin A is highly expressed in clear cell carcinomas of the ovary.
Am J Clin Pathol. 2014; 142(6):830-6 [PubMed] Related Publications
OBJECTIVES: We recently observed expression of the "lung" marker napsin A in ovarian clear cell carcinomas and therefore sought to determine the extent of napsin A expression in a subset of ovarian neoplasms.
METHODS: We identified an archival series of ovarian clear cell carcinomas (n = 36), serous borderline tumors (n = 21), high-grade serous carcinomas (n = 37), and endometrioid adenocarcinomas (n = 29). Using standard immunohistochemical techniques on whole sections of formalin-fixed, paraffin-embedded specimens, we employed a panel of antibodies: napsin A (IP64), estrogen receptor (SP1), WT-1 (6F-H2), PAX-8 (BC12), and TTF-1 (SPT24).
RESULTS: Thirty-six of 36 clear cell carcinomas showed napsin A expression, typically in a uniform pattern. None of the serous borderline tumors or high-grade serous carcinomas manifested napsin A expression. Napsin A was expressed in three (10%) of 29 endometrioid adenocarcinomas, generally in a focal pattern.
CONCLUSIONS: Our study showed that napsin A is an extremely sensitive (100%) marker of ovarian clear cell carcinomas and exhibits very high specificity (100%) in distinguishing clear cell carcinomas from high-grade serous carcinomas and serous borderline tumors and 90% specificity in discriminating clear cell carcinomas from endometrioid carcinomas.

Dai S, Liu J, Sun X, Wang N
Ganoderma lucidum inhibits proliferation of human ovarian cancer cells by suppressing VEGF expression and up-regulating the expression of connexin 43.
BMC Complement Altern Med. 2014; 14:434 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Ganoderma lucidum (G. lucidum, Reishimax) is an herbal mushroom known to have inhibitory effect on tumor cell growth. However, the molecular mechanisms responsible for its anti-proliferative effects on the ovarian cancer have not been fully elucidated.
METHODS: Human ovarian cancer cells HO 8910 (HOCC) and human primary ovarian cells (HPOC) were treated with G. lucidum. Effects of G. lucidum treatment on cell proliferation were studied by MTT assay. The expression of vascular endothelial growth factor (VEGF) and connexin 43 (Cx43) were measured by immunohistochemistry and real time polymerase chain reaction. To study the molecular mechanism of CX43 mediated anti-tumor activity, small interference RNA (siRNA) was used to knockdown Cx43 expression in HOCC.
RESULTS: G. lucidum treatment resulted in reduced proliferation of HOCC. Inhibition of proliferation was accompanied by a decrease in VEGF expression and increase in Cx43 expression in the cancer cells. The extent of immune-reactivity of Cx43 or VEGF in cancer cells were correlated with the concentrations of G. lucidum used for treatment. Furthermore, knockdown of Cx43 expression in HOCC abrogated the effect of G. lucidum on cell proliferation without alteration of G. lucidum-induced attenuation of VEGF expression.
CONCLUSIONS: G. lucidum inhibits ovarian cancer by down-regulating the expression of VEGF and up-regulating the downstream Cx43 expression. G. lucidum may be a promising therapeutic agent for the treatment of ovarian cancer.

Related: GJA1 VEGFA

Bachmann C, Krämer B, Brucker SY, et al.
Relevance of pelvic and para-aortic node metastases in early-stage ovarian cancer.
Anticancer Res. 2014; 34(11):6735-8 [PubMed] Related Publications
AIM: To delineate the relevance of pelvic and para-aortic node involvement in early-stage ovarian cancer.
PATIENTS AND METHODS: Data on 75 consecutive patients with primary stage T1 and 2 ovarian cancer treated at the Department of Gynecology, University Tuebingen, Germany were retrospectively analyzed. All patients underwent stage-related surgery with pelvic and para-aortic lymphadenectomy and adjuvant platinum-based chemotherapy (except pT1aG1). Median follow up was 53.5 months. Clinico-pathological parameters and the distribution pattern of node metastases were evaluated. Statistical analyses were performed using PASW.
RESULTS: Lymph node metastases were detectable in T1 and T2 in 6 (8%) of 75 patients. Three patients (4%) had lymph node metastases in the pelvic nodes only, 2 patients (2.7%) in the para-aortic nodes only; 1 patient (1.3%) both in the pelvic and para-aortic nodes. On multivariate analysis, histological grade 1/ 2 and 3 tumors, serous and endometrioid histology were independent predictors for node metastases, respectively. The risk of relapse was significantly higher with detection of node metastases (p=0.004).
CONCLUSION: A systematic lymphadenectomy in early-stage ovarian cancer leads to an upstaging in a few patients after detection of node metastases even in pelvic or para-aortic nodes, especially in patients with grade 3 tumours and serous cancers. Pelvic and para-aortic lymphadenectomy may detect node involvement in early-stage ovarian cancer and might be helpful in correct staging.

Lazarou A, Fotopoulou C, Coumbos A, et al.
Long-term follow-up of borderline ovarian tumors clinical outcome and prognostic factors.
Anticancer Res. 2014; 34(11):6725-30 [PubMed] Related Publications
AIM: The aim of the present study was to evaluate the characteristics of borderline ovarian tumors (BOTs).
PATIENTS AND METHODS: Data of 151 patients with BOTs were retrospectively evaluated.
RESULTS: A total of 151 cases with BOTs were diagnosed. Histopathological evaluation identified 82.8% with serous, 10.6% with mucinous and 5.3% with mixed histology. Overall, 67.5% had International Federation of Gynecology and Obstetrics (FIGO) stage I, 10.6% FIGO stage II, 14.6% FIGO stage III and 4% FIGO stage IV. A total of 21.9% had peritoneal implants; of which 2.7% were invasive, 17.2% non-invasive and 2% both invasive and non-invasive. Microinvasion was observed in 5.3% and a micropapillary pattern in 12.6%. A total of 12.6% of patients presented second neoplasms. During a median follow-up period of 86 (range=0.1-432) months, there were relapses in 16.8%, of which 52.6% had invasive implants. Overall, 6.2% died of their disease, 28.5% with invasive implants. The median time-to-progression was 48 (range=8-120) months.
CONCLUSION: Patients with BOTs have an excellent prognosis. Long-term follow-up is recommended, since recurrence occurs.

Leung F, Diamandis EP, Kulasingam V
Ovarian cancer biomarkers: current state and future implications from high-throughput technologies.
Adv Clin Chem. 2014; 66:25-77 [PubMed] Related Publications
Ovarian cancer remains the most lethal gynecological malignancy worldwide and survival rates have remained unchanged in spite of medical advancements. Much research has been dedicated to the identification of novel biomarkers for this deadly disease, yet it has not been until recently that a few serum-based tests have been added to carbohydrate antigen 125 as Food and Drug Administration-approved tests for ovarian cancer. This lack of success in identifying clinically relevant biomarkers has been largely attributed to poor study design and bias leading to false discoveries or identification of second-tier biomarkers. Fortunately, a better understanding of the guidelines used to assess the clinical utility of a biomarker and the various phases of biomarker development will aid in avoiding such biases. As well, advances in high-throughput technologies have caused a renewed interest in biomarker discovery for ovarian cancer using alternative strategies such as targeted sequencing and proteomics. In this chapter, we will review the current state of ovarian cancer biomarker research with a focus on diagnostic serum markers. Furthermore, we will examine the standard practice guidelines' criteria for acceptance of a biomarker into the clinic as well as emerging high-throughput approaches to the discovery of novel ovarian cancer biomarkers.

Van Calster B, Van Hoorde K, Valentin L, et al.
Evaluating the risk of ovarian cancer before surgery using the ADNEX model to differentiate between benign, borderline, early and advanced stage invasive, and secondary metastatic tumours: prospective multicentre diagnostic study.
BMJ. 2014; 349:g5920 [PubMed] Free Access to Full Article Related Publications
OBJECTIVES: To develop a risk prediction model to preoperatively discriminate between benign, borderline, stage I invasive, stage II-IV invasive, and secondary metastatic ovarian tumours.
DESIGN: Observational diagnostic study using prospectively collected clinical and ultrasound data.
SETTING: 24 ultrasound centres in 10 countries.
PARTICIPANTS: Women with an ovarian (including para-ovarian and tubal) mass and who underwent a standardised ultrasound examination before surgery. The model was developed on 3506 patients recruited between 1999 and 2007, temporally validated on 2403 patients recruited between 2009 and 2012, and then updated on all 5909 patients.
MAIN OUTCOME MEASURES: Histological classification and surgical staging of the mass.
RESULTS: The Assessment of Different NEoplasias in the adneXa (ADNEX) model contains three clinical and six ultrasound predictors: age, serum CA-125 level, type of centre (oncology centres v other hospitals), maximum diameter of lesion, proportion of solid tissue, more than 10 cyst locules, number of papillary projections, acoustic shadows, and ascites. The area under the receiver operating characteristic curve (AUC) for the classic discrimination between benign and malignant tumours was 0.94 (0.93 to 0.95) on temporal validation. The AUC was 0.85 for benign versus borderline, 0.92 for benign versus stage I cancer, 0.99 for benign versus stage II-IV cancer, and 0.95 for benign versus secondary metastatic. AUCs between malignant subtypes varied between 0.71 and 0.95, with an AUC of 0.75 for borderline versus stage I cancer and 0.82 for stage II-IV versus secondary metastatic. Calibration curves showed that the estimated risks were accurate.
CONCLUSIONS: The ADNEX model discriminates well between benign and malignant tumours and offers fair to excellent discrimination between four types of ovarian malignancy. The use of ADNEX has the potential to improve triage and management decisions and so reduce morbidity and mortality associated with adnexal pathology.

Logan M, Hawkins SM
Role of microRNAs in cancers of the female reproductive tract: insights from recent clinical and experimental discovery studies.
Clin Sci (Lond). 2015; 128(3):153-80 [PubMed] Related Publications
microRNAs (miRNAs) are small RNA molecules that represent the top of the pyramid of many tumorigenesis cascade pathways as they have the ability to affect multiple, intricate, and still undiscovered downstream targets. Understanding how miRNA molecules serve as master regulators in these important networks involved in cancer initiation and progression open up significant innovative areas for therapy and diagnosis that have been sadly lacking for deadly female reproductive tract cancers. This review will highlight the recent advances in the field of miRNAs in epithelial ovarian cancer, endometrioid endometrial cancer and squamous-cell cervical carcinoma focusing on studies associated with actual clinical information in humans. Importantly, recent miRNA profiling studies have included well-characterized clinical specimens of female reproductive tract cancers, allowing for studies correlating miRNA expression with clinical outcomes. This review will summarize the current thoughts on the role of miRNA processing in unique miRNA species present in these cancers. In addition, this review will focus on current data regarding miRNA molecules as unique biomarkers associated with clinically significant outcomes such as overall survival and chemotherapy resistance. We will also discuss why specific miRNA molecules are not recapitulated across multiple studies of the same cancer type. Although the mechanistic contributions of miRNA molecules to these clinical phenomena have been confirmed using in vitro and pre-clinical mouse model systems, these studies are truly only the beginning of our understanding of the roles miRNAs play in cancers of the female reproductive tract. This review will also highlight useful areas for future research regarding miRNAs as therapeutic targets in cancers of the female reproductive tract.

Related: Endometrial (Uterus) Cancer Endometrial Cancer MicroRNAs Cervical Cancer

Abid N, Mnif H, Mellouli M, et al.
Uterine tumour resembling ovarian sex cord tumours presenting as multiple endometrial and cervical uterine polyps: a case report.
Pathologica. 2014; 106(2):73-6 [PubMed] Related Publications
BACKGROUND: Uterine tumours resembling ovarian sex-cord tumours (UTROSCT) are very rare, benign uterine tumours, composed solely of sex cord elements. These tumours have a polyphenotypic immunophentype that favours a derivation from uterine mesenchymal stem cells.
CASE REPORT: A 43-year-old female presented with recurrent vaginal bleeding. On hysteroscopy, she had multiple endometrial and cervical polyps that were removed endoscopically. Histologically, the specimen contained epithelioid cells arranged in tubules, trabeculae and anastomosing cords, without significant cellular atypia or mitotic activity. Immunohistochemical studies were performed. The tumour was found to be diffusely positive for vimentin, calretinin and desmin, focally positive for cytokeratin, CD99 and inhibin and negative for chromogranin and CD10. A subsequent total hysterectomy was performed and revealed neoplastic infiltration of the myometrium.
CONCLUSION: A polyphenotypic immunophenotype is a characteristic feature of UTROSCT, and may be helpful in diagnosis and in exclusion of other lesions. Familiarity with this tumour by gynaecologists and pathologists is essential to avoid misdiagnosis:correct diagnosis of this neoplasm is important in patient management.

Related: Endometrial (Uterus) Cancer Endometrial Cancer Cervical Cancer

Wright AA, Hatfield LA, Earle CC, Keating NL
End-of-life care for older patients with ovarian cancer is intensive despite high rates of hospice use.
J Clin Oncol. 2014; 32(31):3534-9 [PubMed] Article available free on PMC after 01/11/2015 Related Publications
PURPOSE: To date, few studies have examined end-of-life care for patients with ovarian cancer. One study documented increased hospice use among older patients with ovarian cancer from 2000 to 2005. We sought to determine whether increased hospice use was associated with less-intensive end-of-life medical care.
PATIENTS AND METHODS: We identified 6,956 individuals age ≥ 66 years living in SEER areas who were enrolled in fee-for-service Medicare, diagnosed with epithelial ovarian cancer between 1997 and 2007, and died as a result of ovarian cancer by December 2007. We examined changes in medical care during patients' last month of life over time.
RESULTS: Between 1997 and 2007, hospice use increased significantly, and terminal hospitalizations decreased (both P < .001). However, during this time, we also observed statistically significant increases in intensive care unit admissions, hospitalizations, repeated emergency department visits, and health care transitions (all P ≤ .01). In addition, the proportion of patients referred to hospice from inpatient settings rose over time (P = .001). Inpatients referred to hospice were more likely to enroll in hospice within 3 days of death than outpatients (adjusted odds ratio, 1.36; 95% CI, 1.12 to 1.66).
CONCLUSION: Older women with ovarian cancer were more likely to receive hospice services near death and less likely to die in a hospital in 2007 compared with earlier years. Despite this, use of hospital-based services increased over time, and patients underwent more transitions among health care settings near death, suggesting that the increasing use of hospice did not offset intensive end-of-life care.

Related: USA

Zhao M, Ding JX, Nie GY, et al.
HTRA3 is reduced in ovarian cancers regardless of stage.
Cancer Invest. 2014; 32(9):464-9 [PubMed] Related Publications
Ovarian cancer is the leading cause of death in gynaecological cancers. The high temperature requirement factor A3 (HtrA3) is involved in the pathogenesis of ovarian cancer. In this study we investigated whetherHtrA3 protein levels were altered in subtypes of ovarian cancer and whether HtrA3 down-regulation was associated with peritoneal metastasis. Ovarian cancer tissues from 89 patients were analyzed by immunohistochemistry. The levels of HtrA3 protein were lower in all subtypes of ovarian cancer and the lowest levels of HtrA3 were in epithelial ovarian cancer. The down-regulation of HtrA3 levels was not correlated with peritoneal metastasis of epithelial ovarian cancer.

Takeshita T, Ninoi T, Maebayashi T, et al.
Diffusion-weighted magnetic resonance imaging findings in a patient with struma ovarii.
Osaka City Med J. 2014; 60(1):45-52 [PubMed] Related Publications
In this report, the magnetic resonance imaging (MRI) appearance of struma ovarii (SO) in a patient who underwent diffusion-weighted imaging (DWI) of the pelvis and subsequent histological analysis is described. The solid portion of SO showed a high apparent diffusion coefficient (ADC) value, indicating unrestricted diffusion, and each loculus of SO showed different ADC values due to the different viscosity of the cyst contents in each loculus. These unique and characteristic DWI findings may serve as a helpful sign in making the correct diagnosis of SO when DWI findings are interpreted in conjunction with conventional MRI findings.

Engelberth SA, Hempel N, Bergkvist M
Development of nanoscale approaches for ovarian cancer therapeutics and diagnostics.
Crit Rev Oncog. 2014; 19(3-4):281-315 [PubMed] Article available free on PMC after 01/11/2015 Related Publications
Ovarian cancer is the deadliest of all gynecological cancers and the fifth leading cause of death due to cancer in women. This is largely due to late-stage diagnosis, poor prognosis related to advanced-stage disease, and the high recurrence rate associated with development of chemoresistance. Survival statistics have not improved significantly over the last three decades, highlighting the fact that improved therapeutic strategies and early detection require substantial improvements. Here, we review and highlight nanotechnology-based approaches that seek to address this need. The success of Doxil, a PEGylated liposomal nanoencapsulation of doxorubicin, which was approved by the FDA for use on recurrent ovarian cancer, has paved the way for the current wave of nanoparticle formulations in drug discovery and clinical trials. We discuss and summarize new nanoformulations that are currently moving into clinical trials and highlight novel nanotherapeutic strategies that have shown promising results in preclinical in vivo studies. Further, the potential for nanomaterials in diagnostic imaging techniques and the ability to leverage nanotechnology for early detection of ovarian cancer are also discussed.

Konecny GE, Wang C, Hamidi H, et al.
Prognostic and therapeutic relevance of molecular subtypes in high-grade serous ovarian cancer.
J Natl Cancer Inst. 2014; 106(10) [PubMed] Article available free on PMC after 01/10/2015 Related Publications
Molecular classification of high-grade serous ovarian cancer (HGSOC) using transcriptional profiling has proven to be complex and difficult to validate across studies. We determined gene expression profiles of 174 well-annotated HGSOCs and demonstrate prognostic significance of the prespecified TCGA Network gene signatures. Furthermore, we confirm the presence of four HGSOC transcriptional subtypes using a de novo classification. Survival differed statistically significantly between de novo subtypes (log rank, P = .006) and was the best for the immunoreactive-like subtype, but statistically significantly worse for the proliferative- or mesenchymal-like subtypes (adjusted hazard ratio = 1.89, 95% confidence interval = 1.18 to 3.02, P = .008, and adjusted hazard ratio = 2.45, 95% confidence interval = 1.43 to 4.18, P = .001, respectively). More prognostic information was provided by the de novo than the TCGA classification (Likelihood Ratio tests, P = .003 and P = .04, respectively). All statistical tests were two-sided. These findings were replicated in an external data set of 185 HGSOCs and confirm the presence of four prognostically relevant molecular subtypes that have the potential to guide therapy decisions.

Romanidis K, Nagorni EA, Halkia E, Pitiakoudis M
The role of cytoreductive surgery in advanced ovarian cancer: the general surgeon's perspective.
J BUON. 2014 Jul-Sep; 19(3):598-604 [PubMed] Related Publications
Ovarian cancer is one of the most common and lethal cancers worldwide and is usually diagnosed at advanced stages. A radical and effective management of advanced ovarian cancer is needed. Cytoreductive surgery followed by intravenous chemotherapy is currently the gold standard for the management of this disease. However, the recurrence rates still remain high. The introduction of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) combined with complete cytoreductive surgery is a well-promising approach for advanced-stage disease, as well as for recurrent cases. This review aimed to present the surgical management of advanced ovarian cancer and the recent literature about the role and the therapeutic effectiveness of cytoreduction.

Kasiappan R, Sun Y, Lungchukiet P, et al.
Vitamin D suppresses leptin stimulation of cancer growth through microRNA.
Cancer Res. 2014; 74(21):6194-204 [PubMed] Article available free on PMC after 01/11/2015 Related Publications
Obesity is a pandemic and major risk factor for cancers. The reduction of obesity would have been an effective strategy for cancer prevention, but the reality is that worldwide obesity has kept increasing for decades, remaining a major avoidable cancer risk secondary only to smoke. The present studies suggest that vitamin D may be an effective agent to reduce obesity-associated cancer risks in women. Molecular analyses showed that leptin increased human telomerase reverse transcriptase (hTERT) mRNA expression and cell growth through estrogen receptor-α (ERα) activation in ovarian cancer cells, which was suppressed by 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The suppression was compromised when miR-498 induction by the hormone was depleted with microRNA (miRNA) sponges. In mice, high-fat diet (HFD) stimulation of ovarian tumor growth was remarkably suppressed by 1,25(OH)2D3 analogue EB1089, which was also compromised by miR-498 sponges. EB1089 did not alter HFD-induced increase in serum leptin levels but increased miR-498 and decreased the diet-induced hTERT expression in tumors. Quantitative RT-PCR analyses revealed an inverse correlation between hTERT mRNA and miR-498 in response to 1,25(OH)2D3 in estrogen-sensitive ovarian, endometrial, and breast cancers. The studies suggest that miR-498-mediated hTERT downregulation is a key event mediating the anti-leptin activity of 1,25(OH)2D3 in estrogen-sensitive tumors in women.

Related: Breast Cancer MicroRNAs ESR1 TERT

Hannan A, Awan UE, Siddiqui N, Muzaffar N
Malignant transformations in ovarian teratomas: a report of four cases.
J Pak Med Assoc. 2014; 64(8):946-8 [PubMed] Related Publications
Mature cystic teratoma (MCT) is a common ovarian neoplasm in young females. A secondary malignant transformation occurs rarely in cystic teratomas at an older age. These secondary malignant neoplasms most commonly are squamous cell carcinomas (SCCs). Various mechanisms are reported, but the exact aetiology is unknown. We report three cases of SCC arising in cystic teratoma and one case of papillary thyroid neoplasm as secondary transformation. The SCCs were arising from the cyst wall, while the papillary thyroid malignancy arose from the normal-looking thyroid epithelium. Histologically, all SCC cases were poorly differentiated. Poor prognostic features for secondary transformations include size more than 10 cm, older age and rapid growth. Data is scarce regarding their appropriate treatment. However, surgical debulking is necessary. Platinum-based adjuvant regimens and taxanes are recommended in cases of advanced disease. In this paper we review and share our experience with this rare disorder.

Merid SK, Goranskaya D, Alexeyenko A
Distinguishing between driver and passenger mutations in individual cancer genomes by network enrichment analysis.
BMC Bioinformatics. 2014; 15:308 [PubMed] Article available free on PMC after 01/11/2015 Related Publications
BACKGROUND: In somatic cancer genomes, delineating genuine driver mutations against a background of multiple passenger events is a challenging task. The difficulty of determining function from sequence data and the low frequency of mutations are increasingly hindering the search for novel, less common cancer drivers. The accumulation of extensive amounts of data on somatic point and copy number alterations necessitates the development of systematic methods for driver mutation analysis.
RESULTS: We introduce a framework for detecting driver mutations via functional network analysis, which is applied to individual genomes and does not require pooling multiple samples. It probabilistically evaluates 1) functional network links between different mutations in the same genome and 2) links between individual mutations and known cancer pathways. In addition, it can employ correlations of mutation patterns in pairs of genes. The method was used to analyze genomic alterations in two TCGA datasets, one for glioblastoma multiforme and another for ovarian carcinoma, which were generated using different approaches to mutation profiling. The proportions of drivers among the reported de novo point mutations in these cancers were estimated to be 57.8% and 16.8%, respectively. The both sets also included extended chromosomal regions with synchronous duplications or losses of multiple genes. We identified putative copy number driver events within many such segments. Finally, we summarized seemingly disparate mutations and discovered a functional network of collagen modifications in the glioblastoma. In order to select the most efficient network for use with this method, we used a novel, ROC curve-based procedure for benchmarking different network versions by their ability to recover pathway membership.
CONCLUSIONS: The results of our network-based procedure were in good agreement with published gold standard sets of cancer genes and were shown to complement and expand frequency-based driver analyses. On the other hand, three sequence-based methods applied to the same data yielded poor agreement with each other and with our results. We review the difference in driver proportions discovered by different sequencing approaches and discuss the functional roles of novel driver mutations. The software used in this work and the global network of functional couplings are publicly available at http://research.scilifelab.se/andrej_alexeyenko/downloads.html.

Sehouli J, Reinthaller A, Marth C, et al.
Intra- and postoperative catumaxomab in patients with epithelial ovarian cancer: safety and two-year efficacy results from a multicentre, single-arm, phase II study.
Br J Cancer. 2014; 111(8):1519-25 [PubMed] Article available free on PMC after 14/10/2015 Related Publications
BACKGROUND: This is the first study investigating the safety and efficacy of the trifunctional antibody catumaxomab administered i.p. at the end of cytoreductive surgery and postoperatively prior to standard chemotherapy in patients with primary epithelial ovarian cancer (EOC).
METHODS: Patients received i.p. catumaxomab 10 μg intraoperatively and 10, 20, 50 and 150 μg on days 7, 10, 13 and 16, respectively, postoperatively. After the study, patients received standard chemotherapy and were followed for 23 months. The primary endpoint was the rate of postoperative complications.
RESULTS: Forty-one patients entered the study and were evaluable for safety and 34 were alive at 24 months. Complete tumour resection rate was 68%. Postoperative complications were observed in 51%, the most common anastomotic leakage (7%) and wound infections (5%). The most common catumaxomab-related adverse events were abdominal pain, nausea, vomiting and pyrexia. Thirty-nine percent discontinued catumaxomab therapy, and 98% received chemotherapy post study. Kaplan-Meier estimates of disease-free and overall survival after 24 months were 56% and 85%, respectively.
CONCLUSIONS: Intra- and close postoperative catumaxomab seems feasible, but efficacy and safety were limited by postsurgical complications. In the future prospective trials are needed to investigate the best schedule of integration of catumaxomab into current treatment strategies for EOC.

Teng FF, Kalloger SE, Brotto L, McAlpine JN
Determinants of quality of life in ovarian cancer survivors: a pilot study.
J Obstet Gynaecol Can. 2014; 36(8):708-15 [PubMed] Related Publications
OBJECTIVE: Ovarian cancer treatments and outcomes vary substantially, yielding a diverse group of survivors. Few data exist on quality of life (QoL) concerns and the foremost needs of these patients. Our goal was to conduct a pilot study to determine the QoL needs of ovarian cancer survivors to establish priorities for future interventions.
METHODS: In this cross-sectional study, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ-C30 and OV28) QoL questionnaires and one investigator-derived questionnaire were administered in an outpatient setting. Clinical parameters were abstracted and tested for associations with QoL measures.
RESULTS: A total of 102 women consented to participate and completed all components. Their mean age was 58 years (range 29 to 85), with 80% having epithelial ovarian carcinoma and 66% high-grade serous carcinoma. Women with stage I (28%), II (15%), III (47%), and IV (10%) lesions were represented in the primary treatment (25%), surveillance (46%), recurrent (23%), and palliative (7%) phases of the survivorship continuum. Fifty-one percent characterized their disease burden as "quite a bit" or "very much," and this did not vary by histology or diagnoses. Global QoL did not vary by clinico-pathologic parameters. Cardiovascular and respiratory comorbidities were associated with EORTC scores in physical functioning (P=0.027 for cardiovascular and P=0.041 for respiratory), global QoL (P=0.03 for cardiovascular and P=0.039 for respiratory), and sexual health (P=0.025 for cardiovascular). Task completion/memory/concentration, anxiety, and fatigue were the distress categories given highest priority by respondents.
CONCLUSION: In women with ovarian cancer, clinical factors such as age, stage, and histology did not have a significant impact on QoL. Psychosocial factors have a larger impact on global QoL than physical symptoms.

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