Ovarian serous adenocarcinoma identified during IVF: diagnostic approach, surgical management, and reproductive outcome

BACKGROUND: To present a diagnostic evaluation and treatment strategy for serous adenocarcinoma of the ovary discovered during an in vitro fertilisation (IVF) sequence, and report on reproductive outcome after tumour resection and embryo transfer. CASE PRESENTATION: Cycle monitoring in IVF identified an abnormal ovarian lesion which was subjected to ultrasound-guided needle aspiration. Cytology suggested malignancy, and unilateral oophorectomy was performed after formal staging. After surgery, the patient underwent an anonymous donor oocyte IVF cycle which established a viable twin intrauterine pregnancy. No recurrence of cancer has been detected in the >72 month follow-up interval; mother and twin daughters continue to do well. CONCLUSION: Suspicious adnexal structures noted during controlled ovarian hyperstimulation for IVF warrant assessment, and this report confirms the role of aspiration cytology in such cases. If uterine conservation is possible, successful livebirth can be achieved from IVF if donor oocyes are utilised, as described here

Potential role of miR-9 and miR-223 in recurrent ovarian cancer

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) are small, noncoding RNAs that negatively regulate gene expression by binding to target mRNAs. miRNAs have not been comprehensively studied in recurrent ovarian cancer, yet an incurable disease.</p> <p>Results</p> <p>Using real-time RT-PCR, we obtained distinct miRNA expression profiles between primary and recurrent serous papillary ovarian adenocarcinomas (n = 6) in a subset of samples previously used in a transcriptome approach. Expression levels of top dysregulated miRNA genes, miR-223 and miR-9, were examined using TaqMan PCR in independent cohorts of fresh frozen (n = 18) and FFPE serous ovarian tumours (n = 22). Concordance was observed on TaqMan analysis for miR-223 and miR-9 between the training cohort and the independent test cohorts. Target prediction analysis for the above miRNA "recurrent metastatic signature" identified genes previously validated in our transcriptome study. Common biological pathways well characterised in ovarian cancer were shared by miR-9 and miR-223 lists of predicted target genes. We provide strong evidence that miR-9 acts as a putative tumour suppressor gene in recurrent ovarian cancer. Components of the miRNA processing machinery, such as Dicer and Drosha are not responsible for miRNA deregulation in recurrent ovarian cancer, as deluded by TaqMan and immunohistochemistry.</p> <p>Conclusion</p> <p>We propose a miRNA model for the molecular pathogenesis of recurrent ovarian cancer. Some of the differentially deregulated miRNAs identified correlate with our previous transcriptome findings. Based on integrated transcriptome and miRNA analysis, miR-9 and miR-223 can be of potential importance as biomarkers in recurrent ovarian cancer.</p

CD10 − /ALDH − Cells are the Sole Cisplatin-Resistant Component of a Novel Ovarian Cancer Stem Cell Hierarchy

AbstractIt is long established that tumour-initiating cancer stem cells (CSCs) possess chemoresistant properties. However, little is known of the mechanisms involved, particularly with respect to the organisation of CSCs as stem-progenitor-differentiated cell hierarchies. Here we aimed to elucidate the relationship between CSC hierarchies and chemoresistance in an ovarian cancer model. Using a single cell-based approach to CSC discovery and validation, we report a novel, four-component CSC hierarchy based around the markers cluster of differentiation 10 (CD10) and aldehyde dehydrogenase (ALDH). In a change to our understanding of CSC biology, resistance to chemotherapy drug cisplatin was found to be the sole property of CD10−/ALDH− CSCs, while all four CSC types were sensitive to chemotherapy drug paclitaxel. Cisplatin treatment quickly altered the hierarchy, resulting in a three-component hierarchy dominated by the cisplatin-resistant CD10−/ALDH− CSC. This organisation was found to be hard-wired in a long-term cisplatin-adapted model, where again CD10−/ALDH− CSCs were the sole cisplatin-resistant component, and all CSC types remained paclitaxel-sensitive. Molecular analysis indicated that cisplatin resistance is associated with inherent- and adaptive-specific drug efflux and DNA-damage repair mechanisms. Clinically, low CD10 expression was consistent with a specific set of ovarian cancer patient samples. Collectively, these data advance our understanding of the relationship between CSC hierarchies and chemoresistance, which was shown to be CSC- and drug-type specific, and facilitated by specific and synergistic inherent and adaptive mechanisms. Furthermore, our data indicate that primary stage targeting of CD10−/ALDH− CSCs in specific ovarian cancer patients in future may facilitate targeting of recurrent disease, before it ever develops.</jats:p

The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer

The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic), whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05), indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2) cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact/functioning TLR4/MyD88 pathway is required for acquisition of the chemoresistant phenotype. Ex vivo manipulation of ovarian cancer stem cell (CSC) differentiation can decrease MyD88 expression, providing a potentially valuable CSC model for ovarian cancer

Patient Reported Outcomes From CCTG CX.5 (SHAPE): Randomized Trial Comparing Radical Hysterectomy (RH) And Pelvic Node Dissection (PND) Vs Simple Hysterectomy (SH) And PND In Women With Low-Risk Early-Stag

peer reviewe

An International Randomized Phase III Trial Comparing Radical Hysterectomy and Pelvic Node Dissection (RH) vs Simple Hysterectomy and Pelvic Node Dissection (SH) in Patients with Low-Risk Early-Stage Cervical Cancer (LRESCC). A Gynecologic Cancer Intergroup Study led by Canadian Cancer Trials Group (CCTG CX.5-SHAPE).

peer reviewe

Accuracy of Opportunistic Bone Mineral Density Assessment on Staging Computed Tomography for Gynaecological Cancers

Background and Objectives: Women with gynecological cancers constitute a high-risk cohort for loss of bone density. International guidance stipulates women undergoing cancer treatments associated with bone loss should have a quantitative assessment of bone density. Access to Dual-energy X-ray Absorptiometry (DXA) is limited. This study aimed to assess the accuracy of opportunistic bone density measurement on staging computed tomography (CT) scans for gynaecological malignancies, in comparison to the gold standard DXA. Materials and Methods: Women with a staging CT scan of the abdomen and pelvis for a new diagnosis of gynecological cancer were recruited. DXA was performed within 6 weeks of treatment for gynaecological cancer. Lumbar bone density was measured by CT attenuation values, in Hounsfield units (HU), of the anterior trabecular region. Correlations between CT and DXA parameters were analysed. Receiver Operating Characteristic(ROC) curves for diagnosis of low bone density and osteoporosis were analysed. Results: Final cohort included 48 of 50 women recruited. There was good diagnostic accuracy for abnormal bone density and osteoporosis, with areas under the ROC curve at L1 of 0.77 (p = 0.002) and 0.80 (p = 0.020) respectively. CT-HU of 170&ndash;190 yielded sensitivities of 87&ndash;90%, positive predictive values of 75&ndash;84% and negative predictive values of 71&ndash;75% for the diagnosis of low bone mineral density. CT-HU of 90&ndash;110 yielded specificities of 85&ndash;93% for the diagnosis of osteoporosis. Moderate correlations were found between CT-HU and both DXA T-scores and diagnostic categories. Conclusions: This is the first study to assess the opportunistic application of CT in the assessment of bone health in women with gynaecological cancer, a cohort at high-risk of osteoporosis. The correlation between bone density assessment in CT-HU and DXA, and strong AUC values for the diagnosis of low bone density (0.77) and osteoporosis (0.80) support this pragmatic solution in resolving the care-gap in cancer treatment-induced bone loss, often associated with poor access to DXA