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).

Rotruck S, Wilson JT, McGuire J
Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: a case report.
AANA J. 2014; 82(2):140-3 [PubMed] Related Publications
Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) is a complex procedure used for the treatment of various types of cancer. Specifically, HIPEC has shown success where treatment failure sites (metastases) thrive. A classic example of one such area is the peritoneal surface, which remains a prominent failure site for patients with gynecologic and gastrointestinal cancer. Traditionally, most patients with advanced stages of cancer have undergone palliative procedures as part of their treatment modality or had no surgery at all. With the advent of cytoreductive surgery with HIPEC, patients with peritoneal cancer have shown increased survival rates. Anesthetic complications are common during this procedure with disturbances in hemodynamics, coagulation, and respiratory gas exchange. A knowledge of what to anticipate anesthetically will guide the practitioner to achieve successful management during and after the case. In this case report, a 71-year-old woman was treated for stage Ill peritoneal and ovarian cancer by cytoreductive surgery with HIPEC.

Baandrup L, Friis S, Dehlendorff C, et al.
Prescription use of paracetamol and risk for ovarian cancer in Denmark.
J Natl Cancer Inst. 2014; 106(6):dju111 [PubMed] Related Publications
It has been suggested that paracetamol reduces the risk for ovarian cancer. We examined the association between prescription use of paracetamol and ovarian cancer risk in a nationwide case-control study nested within the Danish female population. Case patients (n = 3471) were all women with a first diagnosis of epithelial ovarian cancer during the period from 2000 to 2009. Population control subjects (n = 50576) were selected by risk set sampling. Data were derived from prescription and other nationwide registries. Conditional logistic regression was used to estimate odds ratios (ORs) and two-sided 95% confidence intervals (CIs) for ovarian cancer associated with use of paracetamol or nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs). All statistical tests were two-sided. Use of paracetamol was associated with a reduced odds ratio for ovarian cancer (OR = 0.82; 95% CI = 0.74 to 0.92; P < .001) compared with nonuse, and the odds ratio decreased further with long-term (≥10 years), high-intensity paracetamol use (OR = 0.45; 95% CI = 0.24 to 0.86; P = .02). Use of nonaspirin NSAIDs was not associated with ovarian cancer risk.

Lee JM, Hays JL, Annunziata CM, et al.
Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses.
J Natl Cancer Inst. 2014; 106(6):dju089 [PubMed] Article available free on PMC after 01/06/2015 Related Publications
BACKGROUND: Olaparib has single-agent activity against breast/ovarian cancer (BrCa/OvCa) in germline BRCA1 or BRCA2 mutation carriers (gBRCAm). We hypothesized addition of olaparib to carboplatin can be administered safely and yield preliminary clinical activity.
METHODS: Eligible patients had measurable or evaluable disease, gBRCAm, and good end-organ function. A 3 + 3 dose escalation tested daily oral capsule olaparib (100 or 200mg every 12 hours; dose level1 or 2) with carboplatin area under the curve (AUC) on day 8 (AUC3 day 8), then every 21 days. For dose levels 3 to 6, patients were given olaparib days 1 to 7 at 200 and 400 mg every 12 hours, with carboplatin AUC3 to 5 on day 1 or 2 every 21 days; a maximum of eight combination cycles were permitted, after which daily maintenance of olaparib 400mg every12 hours continued until progression. Dose-limiting toxicity was defined in the first two cycles. Peripheral blood mononuclear cells were collected for polymorphism analysis and polyADP-ribose incorporation. Paired tumor biopsies (before/after cycle 1) were obtained for biomarker proteomics and apoptosis endpoints.
RESULTS: Forty-five women (37 OvCa/8 BrCa) were treated. Dose-limiting toxicity was not reached on the intermittent schedule. Expansion proceeded with olaparib 400mg every 12 hours on days 1 to 7/carboplatin AUC5. Grade 3/4 adverse events included neutropenia (42.2%), thrombocytopenia (20.0%), and anemia (15.6%). Responses included 1 complete response (1 BrCa; 23 months) and 21 partial responses (50.0%; 15 OvCa; 6 BrCa; median = 16 [4 to >45] in OvCa and 10 [6 to >40] months in BrCa). Proteomic analysis suggests high pretreatment pS209-eIF4E and FOXO3a correlated with duration of response (two-sided P < .001; Pearson's R (2) = 0.94).
CONCLUSIONS: Olaparib capsules 400mg every 12 hours on days 1 to 7/carboplatin AUC5 is safe and has activity in gBRCAm BrCa/OvCa patients. Exploratory translational studies indicate pretreatment tissue FOXO3a expression may be predictive for response to therapy, requiring prospective validation.

Related: Breast Cancer Carboplatin

Zhou F, Ma M, Tao G, et al.
Detection of circulating methylated opioid binding protein/cell adhesion molecule-like gene as a biomarker for ovarian carcinoma.
Clin Lab. 2014; 60(5):759-65 [PubMed] Related Publications
BACKGROUND: Hypermethylation of the opioid binding protein/cell adhesion molecule-like (OPCML) gene is frequently observed in ovarian carcinoma. We evaluated the detection of circulating hypermethylated OPCML for detecting ovarian carcinoma and assessing its prognosis.
METHODS: We studied 85 tissue samples including 45 ovarian cancer tissues and 40 normal ovarian tissues and blood samples from 45 ovarian cancer patients and 20 healthy individuals. Bisulfite sequencing and methylation-sensitive restriction enzyme-PCR (MSRE-PCR) were used to detect the frequency of OPCML hypermethylation.
RESULTS: We detected that the frequency of OPCML hypermethylation for tissue and serum samples in ovarian carcinoma were 86.7% (39/45) and 80.0% (36/45), respectively, but none was detected in ovarian tissue and serum of healthy individuals. The frequency of OPCML hypermethylation in endometrioid carcinoma, serous cystadenocarcinoma, mucinous cystadenocarcinoma, clear cell carcinoma, and undifferentiated carcinoma were 80.0%, 85.5%, 50.0%, 80.0%, and 100%, respectively (p > 0.05). The frequencies of OPCML hypermethylation in patients were also different in terms of tumor differentiation degree. We detected hypermethylated OPCML in the sera of 50% of well differentiated, 62.5% of moderately differentiated, 93.1% of poorly differentiated tumors (p < 0.05). The frequency of OPCML hypermethylation at FIGO stage I was 42.9%, stage II was 66.7%, stage III was 85.7%, stage IV was 100% (p < 0.05).
CONCLUSIONS: Detection OPCML methylation in the serum is useful for ovarian carcinoma diagnosis.

Friebel TM, Domchek SM, Rebbeck TR
Modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: systematic review and meta-analysis.
J Natl Cancer Inst. 2014; 106(6):dju091 [PubMed] Article available free on PMC after 01/06/2015 Related Publications
BACKGROUND: There is substantial variability in cancer risk in women who have inherited a BRCA1 or BRCA2 (BRCA1/2) mutation. Numerous factors have been hypothesized to modify these risks, but studies are of variable quality, and it remains unclear which of these may be of value in clinical risk assessment.
METHODS: PubMed and Web of Science databases were searched for articles published through September 2013. Fixed effects meta-analysis was done using the hazard ratios and/or odds ratios to estimate the pooled effect estimates (ES) and 95% confidence intervals (CIs) to identify factors that are associated with cancer risk modification in BRCA1/2 mutation carriers.
RESULTS: We identified 44 nonoverlapping studies that met predefined quality criteria. Sufficient evidence is available to make clinically relevant inferences about a number of cancer risk modifiers. The only variable examined that produced a probable association was late age at first live birth, a meta-analysis showed a decrease in the risk of breast cancer in BRCA1 mutation carriers with women aged 30 years or older vs. women younger than 30 years (ES = 0.65; 95% CI =0.42 to 0.99). The same was shown for women aged 25 to 29 years versus those aged less than 25 years (ES = 0.69; 95% CI = 0.48 to 0.99). Breastfeeding and tubal ligation were associated with reduced ovarian cancer risk in BRCA1 mutation carriers; oral contraceptives were associated with reduced risk among BRCA1/2 mutation carriers. Smoking was associated with increased breast cancer risk in BRCA2 mutation carriers only.
CONCLUSIONS: Data assessing many potential risk modifiers are inadequate, and many have not been externally validated. Although additional studies are required to confirm some associations, sufficient information is available for some risk factors to be used in risk counseling or lifestyle modification to minimize cancer risk in BRCA1/2 mutation carriers

Related: Breast Cancer

Rabban JT, Garg K, Crawford B, et al.
Early detection of high-grade tubal serous carcinoma in women at low risk for hereditary breast and ovarian cancer syndrome by systematic examination of fallopian tubes incidentally removed during benign surgery.
Am J Surg Pathol. 2014; 38(6):729-42 [PubMed] Related Publications
Early detection of sporadic pelvic serous carcinoma remains an elusive goal. In women at high risk for hereditary breast and ovarian cancer syndrome who undergo prophylactic salpingectomy, systematic pathologic examination of the fallopian tubes will detect occult tubal cancer, mostly in the fimbriae, of a minority of women. Such tubal cancers are the putative precursor to advanced-stage pelvic cancer. We hypothesized that early tubal cancer detection can also be accomplished in women at low risk using a similar approach. In this study, we performed complete and systematic examination of the fallopian tubes removed during surgery performed for benign indications. Among 522 women, 4 cases of serous tubal intraepithelial carcinoma (STIC) were identified. Three of these cases would have gone undetected using the current standard of care of sampling only a single random section of the tube. The fourth case was accompanied by occult ovarian carcinoma. The fimbriae contained STIC in 3 of the 4 cases and atypical mucosa in 1 case in which the STIC was in the nonfimbriated portion of the tube. The morphologic and immunohistochemical features (aberrant p53 and MIB-1) of these STICs were similar to those expected in high-risk women. All 4 patients with STIC underwent BRCA1 and BRCA2 gene testing; no germline mutations were identified in any patient. An additional 11 specimens contained atypical mucosal proliferations that fell short of morphologic and immunohistochemical criteria for STIC. Two of these 11 fulfilled criteria for a serous tubal intraepithelial lesion, and the remaining atypical proliferations exhibited normal p53 and MIB-1. For most specimens, the fimbriae could be completely submitted in 1 or 2 cassettes per tube. These results demonstrate that systematic examination of the tubal fimbriae can serve as a form of early detection of sporadic tubal cancer without incurring significant labor or cost. We propose that the tubal fimbriae should be completely examined in all patients undergoing benign surgery even if there are no clinical features to suggest risk for hereditary breast and ovarian cancer syndrome.

Related: Cancer Screening and Early Detection Fallopian Tube Cancer MKI67 TP53

Chan KK, Leung TH, Chan DW, et al.
Targeting estrogen receptor subtypes (ERα and ERβ) with selective ER modulators in ovarian cancer.
J Endocrinol. 2014; 221(2):325-36 [PubMed] Related Publications
Ovarian cancer cells express both estrogen receptor α (ERα) and ERβ, and hormonal therapy is an attractive treatment option because of its relatively few side effects. However, estrogen was previously shown to have opposite effects in tumors expressing ERα compared with ERβ, indicating that the two receptor subtypes may have opposing effects. This may explain the modest response to nonselective estrogen inhibition in clinical practice. In this study, we aimed to investigate the effect of selectively targeting each ER subtype on ovarian cancer growth. Ovarian cancer cell lines SKOV3 and OV2008, expressing both ER subtypes, were treated with highly selective ER modulators. Sodium 3'-(1-(phenylaminocarbonyl)-3,4-tetrazolium)-bis(4-methoxy-6-nitro) benzene sulfonic acid hydrate (XTT) assay revealed that treatment with 1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride (MPP) (ERα antagonist) or 2,3-bis(4-hydroxy-phenyl)-propionitrile (DPN) (ERβ agonist) significantly suppressed cell growth in both cell lines. In contrast, 4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT) (ERα agonist) or 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]-pyrimidin-3-yl]phenol (PHTPP) (ERβ antagonist) significantly enhanced cell growth. These results were confirmed on a xenograft model where SKOV3 cells were injected s.c. into ovariectomized mice. We observed that the average size of xenografts in both the DPN-treated group and the MPP-treated group was significantly smaller than that for the vehicle-treated group. In addition, we found that phospho-AKT expressions in SKOV3 cells were reduced by 80% after treatment with MPP and DPN, indicating that the AKT pathway was involved. The combined treatment with MPP and DPN had a synergistic effect in suppressing ovarian cancer cell growth. Our findings indicate that targeting ER subtypes may enhance the response to hormonal treatment in women with ovarian cancer.

Oliver A, Overton C
Detecting ovarian disorders in primary care.
Practitioner. 2014; 258(1769):15-9, 2 [PubMed] Related Publications
Ovarian cysts occur more often in premenopausal than postmenopausal women. Most of these cysts will be benign, with the risk of malignancy increasing with age. The risk of a symptomatic ovarian cyst in a premenopausal female being malignant is approximately 1:1,000 increasing to 3:1,000 at the age of 50. Ovarian cysts may be asymptomatic but presenting symptoms include pelvic pain, pressure symptoms and discomfort and menstrual disturbance. Functional cysts in particular can be linked with irregular vaginal bleeding or menorrhagia. Ovarian torsion is most common in the presence of an ovarian cyst. Dermoid cysts are most likely to tort. Torsion presents with sudden onset of severe colicky unilateral pain radiating from groin to loin. There may be nausea and vomiting. It is often confused with ureteric colic where the pain is similar but radiates loin to groin. Symptoms which may be suggestive of a malignant ovarian cyst, particularly in the over 50 age group, include: weight loss, persistent abdominal distension or bloating, early satiety, pelvic or abdominal pain and increased urinary urgency and frequency. CA125 levels should be checked in women who present with frequent bloating, feeling full quickly, loss of appetite, pelvic or abdominal pain or needing to urinate quickly or urgently. Symptomatic postmenopausal women, those with a cyst > or = 5 cm, or raised CA125 levels, should be referred to secondary care. Functional cysts, particularly when they are < 5 cm diameter, usually resolve spontaneously without the need for intervention. In premenopausal women simple cysts > or = 5 cm are less likely to resolve and need an annual ultrasound assessment as a minimum.

Cruz-Galarza D, Pérez-Rodríguez O, Laboy-Torres J, Gutiérrez-Rivera S
An unusual case of a borderline Brenner tumor associated with bilateral serous cystadenoma and endometrial carcinoma.
Bol Asoc Med P R. 2014; 106(1):54-6 [PubMed] Related Publications
Brenner tumor accounts for 1.5 to 2.5% of ovarian tumors. Nearly all are benign and 1% malignant. Less than twenty-five cases of borderline Brenner tumor have been reported worldwide. Our case is the first one related to a bilateral ovarian serous cystadenofibroma and endometrioid adenocarcinoma. This unusual case increases the limited data for borderline Brenner tumors.

Related: Breast Cancer Endometrial (Uterus) Cancer Endometrial Cancer

Sneesby L
Home is where I want to die: Kelly's journey.
Contemp Nurse. 2014; 46(2):251-3 [PubMed] Related Publications
The definition of a 'good death' is centred on being peaceful, dignified and pain free. The preferred place of death has also been highlighted as an important concept in defining a good death (Cox, Almack, Pollack, & Seymour, 2011). Seventy percent of Australians express the desire to spend their last days at home. In reality only 16% of people die at home (Preferred Place of Death, 2008). With 10% of Australians dying in residential aged care facilities and approximately 20% in hospices, the rest die in hospitals (Parish et al., 2006). Family support and the family's care giving ability play a major role in determining whether a person is able to die at home. Other factors include the availability of medical and nursing care. This story has been written with the consent of Kelly's husband. All efforts have been made to maintain privacy and confidentiality: Pseudonyms have been used.

Related: Australia

Tsubamoto H, Sonoda T, Yamasaki M, Inoue K
Impact of combination chemotherapy with itraconazole on survival of patients with refractory ovarian cancer.
Anticancer Res. 2014; 34(5):2481-7 [PubMed] Related Publications
BACKGROUND: After progression during chemotherapy, persistent ovarian cancer rarely responds to cytotoxic agents. We evaluated the use of adjunctive itraconazole for treating refractory ovarian cancer.
PATIENTS AND METHODS: Medical records of patients with ovarian cancer were retrospectively reviewed to select those with a history of platinum and taxane administration, clinical progression within six months of the last platinum administration, continuation of chemotherapy after the first progression during chemotherapy.
RESULTS: Among 55 patients, itraconazole in combination with chemotherapy was administered to 19 patients. The median progression-free survival (PFS) was 103 days and 53 days for chemotherapy with and without itraconazole, respectively (p=0.014). The corresponding median overall survival was 642 days and 139 days, respectively (p=0.006). The hazard ratio for PFS was 0.24 (p=0.002) and for overall survival was 0.27 (p=0.006) for therapy with itraconazole.
CONCLUSION: Adjunctive itraconazole is promising for patients with refractory ovarian cancer.

Related: Carboplatin

Liu Z, Yamanouchi K, Ohtao T, et al.
High levels of Wilms' tumor 1 (WT1) expression were associated with aggressive clinical features in ovarian cancer.
Anticancer Res. 2014; 34(5):2331-40 [PubMed] Related Publications
AIM: The aim of the present study was to evaluate the correlation between WT1 expression levels and clinical features, to investigate the prognostic value of WT1 expression and to use lentiviral constructs to examine whether overexpression of WT1 affects cell proliferation and invasion in ovarian cancer patients.
MATERIALS AND METHODS: Real-time quantitative PCR (qPCR) methods were employed to analyze WT1 expression levels in clinical samples from 63 patients with ovarian cancer. The correlation between the copy number of WT1 mRNA and clinical variables was analyzed.
RESULTS: The median copy number of WT1 mRNA was 53.94 (range=2.135-32,257) in all subjects and WT1 expression levels were found significantly increased in patients with a higher stage cancer (p<0.05), lymphnode (p<0.001) and omentum metastasis (p<0.001), as well as ascites production (p<0.05), compared to patients lacking these clinical variables. No significant difference in WT1 expression levels were observed between patients with and without recurrence. The median disease-free survival time in patients with low WT1 expression levels was significantly longer (p=0.038) than that in patients with high WT1 expression. However, overall survival curves showed no statistically significant (p=0.457) differences between patients with high- and low-WT1 expression levels. An in vitro study revealed that WT1 over-expression enhanced cell proliferation and invasion in ovarian cancer cells transduced with lentiviral constructs.
CONCLUSION: Using qPCR, we found that high levels of WT1 expression correlated with aggressive clinical features in ovarian cancer. High WT1 expression may impact on median disease-free survival in ovarian cancer.

Related: WT1

Syrios J, Banerjee S, Kaye SB
Advanced epithelial ovarian cancer: from standard chemotherapy to promising molecular pathway targets--where are we now?
Anticancer Res. 2014; 34(5):2069-77 [PubMed] Related Publications
Ovarian cancer is the most frequent cause of death from gynaecological malignancy in the Western countries, and differences in outcome among different histological subtypes are being increasingly recognized. It is generally considered as chemosensitive, but resistant clones evolve in the majority of cases, at varying rates. In this brief review, we describe advances in conventional chemotherapy, particularly the use of weekly paclitaxel. We then focus on new promising agents that target certain pathways which drive the genesis and evolution of ovarian cancer; these include poly(ADP-ribose) polymerase (PARP) inhibitors targeting tumor cells deficient in homologous recombination. We also discuss other targets including the folate receptor. Ovarian cancer has also proved to be one of the most sensitive types of cancer to an anti-angiogenic approach and we summarize recent experience using a range of agents.

Bernard V, Mornstein V, Bourek A
Effect of near field ultrasound on carboplatin treatment of ovarian carcinoma cells.
Indian J Biochem Biophys. 2013; 50(4):284-8 [PubMed] Related Publications
It has long been shown that therapeutic ultrasound has the potential to affect cells surfaces and membranes. In this study, the effects of ultrasound in near field mode, the anti-cancer drug carboplatin and their combined application were studied on human carcinoma cells A2780. Four modes of treatment were used: exposure to ultrasonic field, application of carboplatin, exposure to ultrasound followed by carboplatin and carboplatin treatment followed by exposure to near field ultrasound. The value of viability was measured by standard MTT test. The value of ultrasound intensity was set 1 W x cm(-2) and 1 MHz frequency was used. The real value of acoustic pressure during in vitro experiments was assessed by hydrophone. The results showed that a combined effect of ultrasound and carboplatin influenced the viability of human carcinoma cells A2780 more than the application of ultrasound or carboplatin alone. It could be assumed that exposure of cells to ultrasonic field had an immediate effect on the structure of cell surface and consequently on the entry of carboplatin into the cell. The results of our experiments demonstrated possibility of using therapeutic ultrasound in potentiating the cytostatic treatment of human carcinoma cells.

Related: Carboplatin

Djukic M, Stankovic Z, Vasiljevic M, et al.
Ovary-preserving tumorectomy for immature teratoma in an adolescent--case report.
Eur J Gynaecol Oncol. 2014; 35(2):199-201 [PubMed] Related Publications
The authors present a case of a 14-year-old premenarchal girl with a large solid tumor of the left ovary. The rim of normal ovarian tissue was visible around the tumor on ultrasonography scan. Although the levels of two tumor markers, LDH and CA125, were elevated, the authors performed an organ-sparing tumorectomy. The final pathology report revealed foci of immature neural tissue, with a final diagnosis immature teratoma Stage Ia.

Hacivelioglu S, Erkanli S
A large pedunculated leiomyoma with two-sided cystic degenerations mimicking a bilateral ovarian malignancy: a case report.
Eur J Gynaecol Oncol. 2014; 35(2):192-4 [PubMed] Related Publications
The authors present an unusual case of a large, pedunculated uterine leiomyoma with two-sided cystic degenerations, which mimicked a bilateral malignant ovarian tumor on ultrasonography and magnetic resonance imaging (MRI). A 32-year-old unmarried female patient presented to our outpatient clinic with complaints of abdominal distention and a palpable abdominal mass extending into the upper abdomen. Ultrasonography and MRI revealed a large solid mass with bilateral cystic areas extending into both uterine adnexa. The patient then underwent a laparotomy. Gross examination revealed normal ovaries and a pedunculated mass with two-sided prominent cystic structures originating from the uterine fundus. The tumor was excised through the peduncle and pathologic evaluation revealed a uterine leiomyoma with cystic degenerations. In conclusion, a large, pedunculated leiomyoma with two-sided cystic degenerations can mimic a bilateral malignant ovarian neoplasm on imaging studies. Therefore, uterine leiomyomas with bilateral cystic degenerations should be considered during the differential diagnosis of malignant ovarian masses.

Nakao Y, Yamasaki F, Yokoyama M, et al.
Minimal deviation endometrioid adenocarcinoma of the endometrium and its MRI findings.
Eur J Gynaecol Oncol. 2014; 35(2):185-7 [PubMed] Related Publications
Minimal deviation endometrioid adenocarcinoma (MDA-E) of the endometrium is a rare pathological entity, and its radiological features are rarely documented. A 73-year-old Japanese woman was referred to the authors when an endometrial biopsy revealed moderately differentiated endometrioid adenocarcinoma. Preoperative radiological examinations, including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) showed no evidence of cancer nests. In the hysterectomy specimen, mildly atypical glands were scattered throughout the entire depth of the myometrium, without stromal desmoplastic reaction, and a tiny focus of typical, ruptured, endometrioid adenocarcinoma glands was found in the atrophic endometrium. MRI had not been able to identify this unusual, scattered, myometrial invasion. It should be kept in mind that in cases showing Stage IA endometrial carcinoma without endometrial thickening on MRI, this rare form of invasion may be present.

Related: Endometrial (Uterus) Cancer Endometrial Cancer

Sibio S, Sammartino P, Accarpio F, et al.
Axillary lymph node metastasis as first presentation of peritoneal carcinomatosis from serous papillary ovarian cancer: case report and review of the literature.
Eur J Gynaecol Oncol. 2014; 35(2):170-3 [PubMed] Related Publications
Ovarian cancer usually spreads into abdominal cavity and to the loco-regional lymph nodes. Extra-abdominal metastases are less frequent and isolated axillary metastases are very rare. The authors describe the case of a 49-year-old woman who was diagnosed with a peritoneal carcinomatosis from ovarian cancer by mean of an enlarged axillary lymph node biopsy, whose histological examination identified as a ovarian cancer metastasis. Patient was treated by peritonectomy and intraperitoneal chemohyperthermic perfusion (HIPEC). Although patients with axillary lymph node metastasis from ovarian cancer are though to be metastatic (FIGO Stage IV), surgical radical treatment and adjuvant systemic chemotherapy can achieve the same prognosis of Stage IIIb-c patients, suggesting they could be a particularly good prognosis subset of patients. Early differential diagnosis between ovarian or breast cancer in axillary lymph node metastasis is crucial but not always very simple, because of the very different course and treatment of these tumours.

Kurita T, Nakajima K, Koi C, et al.
Management of a primary retroperitoneal mucinous cystadenocarcinoma: case report.
Eur J Gynaecol Oncol. 2014; 35(2):163-6 [PubMed] Related Publications
PURPOSE: To review the treatment of primary retroperitoneal mucinous cystadenocarcinoma (PRMC).
CASE REPORT: A 30-year-old woman had a large retroperitoneal mucinous adenocarcinoma treated with conservative laparoscopic surgery. Two years later, she was found to have bilateral ovarian cysts at the time of cesarean section. Since cystectomies revealed mucinous adenocarcinoma, she underwent complete surgical staging and adjuvant chemotherapy at this time.
CONCLUSION: A rare case of similar cancer in the ovary following treatment for PRMC was described. It is unclear whether the prognosis is improved by oophorectomy. Further cases and long-term follow-up are necessary.

Ozalp SS, Yalcin OT, Telli E, et al.
Borderline ovarian tumors: outcomes of fertility sparing surgery.
Eur J Gynaecol Oncol. 2014; 35(2):154-6 [PubMed] Related Publications
AIM: Borderline ovarian tumors(BOT) account for ten to 20 percent of all epitelial ovarian carcinomas and often occur in reproductive ages. The aim of this study was to evaluate the clinical and reproductive outcomes of patients who were diagnosed with BOT and underwent fertility sparing surgery.
MATERIALS AND METHODS: Patients younger than 40 years who underwent fertility sparing surgery for BOT from 2004 to 2012 were reviewed retrospectively and were evaluated according to the reproductive and clinical outcomes.
RESULTS: Twenty-eight patients younger than 40 years with BOT underwent fertility sparing surgery. Median follow up time was 42 +/- 28.1 months. During the follow up period, two patients (7.1%) developed recurrence at 35 and 36 months, respectively. Five (17.9%) out of 28 patients became pregnant during the follow up period.
CONCLUSION: Fertility sparing surgery should be the first choice for the treatment of BOT in patients who wish to preserve fertility.

Wong LF, Wahab NA, Gleeson N
Appendectomy with cytoreductive surgery for ovarian and type 2 endometrial carcinoma.
Eur J Gynaecol Oncol. 2014; 35(2):143-8 [PubMed] Related Publications
UNLABELLED: There is considerable variation within and between cancer centers in the practice of appendectomy as part of cytoreductive surgery for ovarian carcinoma and in the surgical staging of endometrial carcinoma. The purpose of this study was to determine the prevalence and the type of appendiceal pathology, the morbidity associated with appendectomy in gynaecologic cancer surgery.
MATERIALS AND METHODS: This is a retrospective review of all cytoreductive surgery for ovarian carcinoma and surgical staging for endometrial carcinoma with appendectomy over a four year period.
RESULTS: Two hundred and fifty-one patients (38 patients for endometrial carcinoma surgery and 213 patients for ovarian cytoreduction) had an appendectomy performed. Metastases to the appendix was present in 46 (23.2%) of primary ovarian carcinoma and one (2.6%) primary endometrial carcinosarcoma. The appendix was more likely to be involved in advanced stage ovarian cancer with positive peritoneal washings, omental deposits, grade 3 differentiation, and papillary serous histology. Sixteen (6.4%) co-incidental primary appendiceal tumours were detected. No postoperative morbidity specific to appendectomy was identified. One case of ovarian carcinoma was upstaged from IC to IIIA by the appendiceal metastases. There was no upstaging of disease in the endometrial carcinoma group.
DISCUSSION: Appendectomy is an integral part of ovarian cytoreductive surgery but the authors found it did not upstage the disease in a clinically significant manner. The incidence of co-incidental appendiceal primary tumours was high in this series and may add value to the procedure in preventing further surgeries. The absence of procedure related morbidity is reassuring. The authors recommend appendectomy for all ovarian staging surgery and its consideration in type 2 endometrial cancer.

Related: Gastrointestinal Carcinoid Tumours Endometrial (Uterus) Cancer Endometrial Cancer

Taskiran C, Erdem O, Onan A, et al.
Maspin expression in endometrial hyperplasia and carcinoma, and its relation with angiogenesis.
Eur J Gynaecol Oncol. 2014; 35(2):134-9 [PubMed] Related Publications
AIM: The purpose of this study was to evaluate the maspin expression in endometrial hyperplasia and cancer, and also to investigate its relation with angiogenesis.
MATERIALS AND METHODS: A total of 19 women with complex atypical hyperplasia, 44 patients with simple hyperplasia without atypia, and 67 patients with endometrial carcinoma were included. Maspin expression was assessed by immunohistochemistry (IHC), and tested for possible significant relation with age, FIGO stage, histologic type, grade, depth of myometrial invasion (MI), lymphovascular space involvement (LVSI), lymph node metastasis, and overall survival (OS). Angiogenesis was determined by vascular endothelial growth factor (VEGF) staining.
RESULTS: Maspin expression was detected in only three patients with endometrial hyperplasia (5%). In patients with endometrial cancer, cytoplasmic and nuclear maspin expressions were detected in 36 (53.7%) and 18 (26.9%) patients, respectively. No significant relation was noted between staining localizations and prognostic variables. The five-year OS rate for patients with cytoplasmic staining was 91%, compared to 87% for patients without staining (p = 0.31). These values for nuclear expression were 100% and 87%, respectively (p = 0.16). The cytoplasmic and nuclear maspin expressions were found to be significantly correlated with VEGF (r = 0.278, p = 0.02 and r = 0.295, p = 0.01, respectively).
DISCUSSION: This is the first study to demonstrate the relation between maspin expression and angiogenesis in endometrial cancer. Although no survival difference was noted for cytoplasmic or nuclear maspin expressions, a tendency was detected for nuclear staining. Further series will clarify the exact prognostic role of maspin expression in gynecological malignancies including endometrial cancer.

Related: Endometrial (Uterus) Cancer Endometrial Cancer Angiogenesis and Cancer VEGFA SERPINB5

Koh YV, Tang JI, Choo BA, et al.
Adjuvant radiotherapy for endometrial cancer--a comparative review of radiotherapy technique with acute toxicity.
Eur J Gynaecol Oncol. 2014; 35(2):128-33 [PubMed] Related Publications
OBJECTIVES: The addition of pelvic radiotherapy to brachytherapy (EBRT-BT) in early-stage endometrial cancer is controversial and may cause unnecessary toxicity. The incidence of acute toxicity of EBRT-BT will have an impact on clinical decision and patient compliance but is currently poorly understood. This study compares the acute toxicities of EBRT-BT versus BT alone.
MATERIALS AND METHODS: Seventy-nine patients with FIGO Stage IA-II endometrial cancer who underwent adjuvant radiotherapy, (EBRT-BT or BT alone) from 2001 to 2011 were included in the study. Medical records of these patients were reviewed retrospectively and toxicity graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Patients were followed up for at least three months post-treatment to assess resolution of toxicity.
RESULTS: The mean age of the study group was 60.6 years. Median follow-up was four years. Forty patients received EBRT-BT. There was a 37% increase in Grade 1-3 diarrhea with the addition of pelvic radiotherapy (OR 18.67, p < 0.0005) and a 34% increase in lethargy (p < 0.0005). There was also an increased occurrence of genitourinary and skin toxicities. Two patients in the EBRT-BT group required hospitalisation for severe diarrhea and three patients were unable to complete the treatment. All acute toxicities had resolved by three months post treatment.
CONCLUSION: EBRT-BT causes significantly more acute toxicities compared to BT alone. Patients should be informed of this during counselling.

Related: Brachytherapy Endometrial (Uterus) Cancer Endometrial Cancer

Singh SD, Ryerson AB, Wu M, Kaur JS
Ovarian and uterine cancer incidence and mortality in American Indian and Alaska Native women, United States, 1999-2009.
Am J Public Health. 2014; 104 Suppl 3:S423-31 [PubMed] Article available free on PMC after 01/06/2015 Related Publications
OBJECTIVES: We examined geographic differences and trends in incidence and mortality of ovarian and uterine cancer in American Indian/Alaska Native (AI/AN) women.
METHODS: We linked mortality data (1990-2009) and incidence data (1999-2009) to Indian Health Service (IHS) records. Death (and incidence) rates for ovarian and uterine cancer were examined for AI/AN and White women; Hispanics were excluded. Analyses focused on Contract Health Service Delivery Area (CHSDA) counties.
RESULTS: AI/AN and White women had similar ovarian and uterine cancer death rates. Ovarian and uterine cancer incidence and death rates were higher for AI/ANs residing in CHSDA counties than for all US counties. We also observed geographic differences, regardless of CHSDA residence, in ovarian and uterine cancer incidence and death rates in AI/AN women by IHS region; Pacific Coast and Southern Plains women had higher ovarian cancer death rates and Northern Plains women had higher uterine cancer death rates.
CONCLUSIONS: Regional differences in the incidence and mortality of ovarian and uterine cancers among AI/AN women in the United States were significant. More research among correctly classified AI/AN women is needed to understand these differences.

Related: USA

Mozos A, Catasús L, D'Angelo E, et al.
The FOXO1-miR27 tandem regulates myometrial invasion in endometrioid endometrial adenocarcinoma.
Hum Pathol. 2014; 45(5):942-51 [PubMed] Related Publications
Micro-RNA (miRNA) signatures influence the prognosis of cancer, but little is known about their role in myometrial invasion in endometrioid endometrial adenocarcinoma (EEC). We studied miRNA expression signatures in noninvasive and invasive EEC focusing on the alteration of miR-27 and its main target, FOXO1 as well as their relationship with the clinicopathological parameters and other genetic alterations such as PIK3CA mutations. In 25 tumors and 5 normal endometria, unsupervised hierarchical clustering analysis showed that normal endometria and noninvasive EEC were grouped together and separately from invasive and advanced stage tumors. Of the 20 miRNAs differentially expressed in noninvasive (stage IA) and myoinvasive adenocarcinomas (stage IB and IC), miR27 was overexpressed in invasive adenocarcinomas, and its expression increased linearly according to stage. Results were validated by quantitative real-time reverse transcription polymerase chain reaction in an independent series of 44 EEC. By in situ hybridization, miR-27 expression was limited to the stroma. Using quantitative real-time reverse transcription polymerase chain reaction, the expression of proapoptotic transcription factor FOXO1 was down-regulated in invasive compared with noninvasive tumors. Furthermore, we found that the expression of active caspase 3 was higher in noninvasive than invasive EEC. When stratified by PIK3CA mutations, all invasive tumors down-regulated FOXO1, but only nonmutated adenocarcinomas showed miR-27 overexpression. In conclusion, we propose that the miR27-FOXO1 tandem inhibits apoptosis and represents an alternative pathway for tumor cell survival in PIK3CA-nonmutated EEC.

Related: Endometrial (Uterus) Cancer Endometrial Cancer

Ekinci T, Ozbay PO, Yiğit S, et al.
The correlation between immunohistochemical expression of MMP-2 and the prognosis of epithelial ovarian cancer.
Ginekol Pol. 2014; 85(2):121-30 [PubMed] Related Publications
OBJECTIVES: The Objectives: The goal of the study was to evaluate the correlation of matrix metalloproteinase-2 (MMP-2) expression with tumor spread, metastasis, survival and recurrence in early and advanced-stage Epithelial Ovarian Cancer (EOC).
MATERIAL AND METHODS: Medical records of patients, hospitalized at the Department of Obstetrics and Gynecology Izmir Atatürk Training and Research Hospital between 2003 and 2008, were reviewed. Patient age, tumor size, localization, histologic type and tumor grade, stage, metastasis status, patient outcomes and follow-up data were obtained from the records of the obstetrics and gynecology clinic, as well as during face-to-face or telephone interviews.
RESULTS: The percentage of MMP-2 staining (expression) in the epithelial cells was not significantly associated with tumor stage and grade, histologic type, tumor diameter recurrence and overall survival (p > 0.05). A significant correlation was found between the percentage of MMP-2 staining (expression) and metastasis status (p < 0.05). The staining intensity of MMP-2 was not significantly associated with tumor stage and grade, diameter recurrence, metastasis and overall survival (p > 0.05), but was with histologic type (p < 0.05). Total scores were not significantly associated with tumor stage and grade, histologic type, tumor diameter recurrence, metastasis and overall survival (p > 0.05). Stromal staining (expression) of MMP-2 was not significantly correlated with tumor stage and grade, histologic type, tumor diameter and outcomes (p > 0.05), but was with recurrence and presence of metastasis (p < 0.05). No significant association was found between the overall survival and percentage of MMP-2 staining (p > 0.05), total score (p > 0.05) and staining intensity (p > 0.05). The association of disease-free survival with the percentage of MMP-2 staining (p > 0.05), total score (p > 0.05), staining intensity (p > 0.05) and stromal staining (p > 0.05) was not statistically significant. The survival of patients with positive stromal staining was significantly shorter compared to cases with negative stromal staining (p < 0.05).
CONCLUSIONS: Large-scale, comprehensive research is needed to verify whether MMP 2 may be used as a routine prognostic factor for EOC.

Related: MMP2

Căpîlna ME, Rusu SC, Szabo B, Marian C
Three synchronous primary pelvic cancers--a case report.
Rev Med Chir Soc Med Nat Iasi. 2014 Jan-Mar; 118(1):107-10 [PubMed] Related Publications
The occurrence of synchronous primary gynaecologic malignancies is a relatively common event. However, the occurrence of three different pelvic cancers is very rare. In this report, we describe the clinical, surgical and pathological findings of a patient with synchronous primary malignancies of the fallopian tube, endometrium and sigmoid colon. To our knowledge, it is the first case described in the literature with such an association of primary synchronous cancers.

Related: Carboplatin Endometrial (Uterus) Cancer Endometrial Cancer Fallopian Tube Cancer

Schmit F, Utermark T, Zhang S, et al.
PI3K isoform dependence of PTEN-deficient tumors can be altered by the genetic context.
Proc Natl Acad Sci U S A. 2014; 111(17):6395-400 [PubMed] Article available free on PMC after 29/10/2014 Related Publications
There has been increasing interest in the use of isoform-selective inhibitors of phosphatidylinositide-3-kinase (PI3K) in cancer therapy. Using conditional deletion of the p110 catalytic isoforms of PI3K to predict sensitivity of cancer types to such inhibitors, we and others have demonstrated that tumors deficient of the phosphatase and tensin homolog (PTEN) are often dependent on the p110β isoform of PI3K. Because human cancers usually arise due to multiple genetic events, determining whether other genetic alterations might alter the p110 isoform requirements of PTEN-null tumors becomes a critical question. To investigate further the roles of p110 isoforms in PTEN-deficient tumors, we used a mouse model of ovarian endometrioid adenocarcinoma driven by concomitant activation of the rat sarcoma protein Kras, which is known to activate p110α, and loss of PTEN. In this model, ablation of p110β had no effect on tumor growth, whereas p110α ablation blocked tumor formation. Because ablation of PTEN alone is often p110β dependent, we wondered if the same held true in the ovary. Because PTEN loss alone in the ovary did not result in tumor formation, we tested PI3K isoform dependence in ovarian surface epithelium (OSE) cells deficient in both PTEN and p53. These cells were indeed p110β dependent, whereas OSEs expressing activated Kras with or without PTEN loss were p110α dependent. Furthermore, isoform-selective inhibitors showed a similar pattern of the isoform dependence in established Kras(G12D)/PTEN-deficient tumors. Taken together, our data suggest that, whereas in some tissues PTEN-null tumors appear to inherently depend on p110β, the p110 isoform reliance of PTEN-deficient tumors may be altered by concurrent mutations that activate p110α.

Related: PTEN

Coleman RL, Moon J, Sood AK, et al.
Randomised phase II study of docetaxel plus vandetanib versus docetaxel followed by vandetanib in patients with persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma: SWOG S0904.
Eur J Cancer. 2014; 50(9):1638-48 [PubMed] Related Publications
BACKGROUND: Vandetanib is an oral tyrosine kinase inhibitor of VEGFR-2/3, EGFR and RET, which has demonstrated clinical activity as a single agent and in combination with taxanes. We explored the efficacy, safety and toxicity of docetaxel and vandetanib in women with recurrent ovarian cancer (OC).
METHODS: Women with refractory or progressive OC were randomised 1:1 to docetaxel (75 mg/m(2), IV)+vandetanib (100mg daily, PO, D+V) or docetaxel (75 mg/m(2), D). Up to three additional cytotoxic regimens for recurrence and prior anti-angiogenic agents (as primary therapy) were allowed. The primary end-point was progression free survival (PFS). The study had 84% power to detect a PFS hazard ratio of 0.65, using a one-sided P of 0.1. This corresponds to an increase in median PFS from 3.6 months to 5.6 months. Patients progressing on D were allowed to receive single agent vandetanib (D → V).
RESULTS: 131 Patients were enrolled; two were excluded. 16% had received prior anti-angiogenic therapy. The median PFS estimates were 3.0 mos (D+V) versus 3.5 (D); HR: 0.99 (80% CI: 0.79-1.26). 61 Patients on D+V were assessable for toxicity; 20(33%) had treatment-related Grade (G) 4 events, primarily haematologic. Similarly, 17 (27%) of 64 patients receiving D had G4 events, primarily haematologic. 27 Evaluable patients crossed-over to V. 1/27(4%) experienced a G4 event. G3 diarrhoea was observed in 4% D → V patients. Median OS was 14 mos (D+V) versus 18 mos (D → V); HR(OS): 1.25 (80% CI: 0.93-1.68). Crossover vandetanib response was 4% (1/27 evaluable patients). High plasma IL-8 levels were associated with response to D+V.
CONCLUSIONS: Combination docetaxel+vandetanib did not prolong PFS relative to docetaxel alone in OC patients. No unexpected safety issues were identified.

Related: Fallopian Tube Cancer Docetaxel

Joshi HP, Subramanian IV, Schnettler EK, et al.
Dynamin 2 along with microRNA-199a reciprocally regulate hypoxia-inducible factors and ovarian cancer metastasis.
Proc Natl Acad Sci U S A. 2014; 111(14):5331-6 [PubMed] Article available free on PMC after 08/10/2014 Related Publications
Hypoxia-driven changes in the tumor microenvironment facilitate cancer metastasis. In the present study, we investigated the regulatory cross talk between endocytic pathway, hypoxia, and tumor metastasis. Dynamin 2 (DNM2), a GTPase, is a critical mediator of endocytosis. Hypoxia decreased the levels of DNM2. DNM2 promoter has multiple hypoxia-inducible factor (HIF)-binding sites and genetic deletion of them relieved hypoxia-induced transcriptional suppression. Interestingly, DNM2 reciprocally regulated HIF. Inhibition of DNM2 GTPase activity and dominant-negative mutant of DNM2 showed a functional role for DNM2 in regulating HIF. Furthermore, the opposite strand of DNM2 gene encodes miR-199a, which is similarly reduced in cancer cells under hypoxia. miR-199a targets the 3'-UTR of HIF-1α and HIF-2α. Decreased miR-199a expression in hypoxia increased HIF levels. Exogenous expression of miR-199a decreased HIF, cell migration, and metastasis of ovarian cancer cells. miR-199a-mediated changes in HIF levels affected expression of the matrix-remodeling enzyme, lysyloxidase (LOX). LOX levels negatively correlated with progression-free survival in ovarian cancer patients. These results demonstrate a regulatory relationship between DNM2, miR-199a, and HIF, with implications in cancer metastasis.

Related: HIF1A

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