Research Foundation-Flanders, European Research Council, Charles University, Ministry of Health of the Czech Republic.

Conservative treatment can be proposed to all young patients when tumor is limited to the ovaries, as ovarian recurrences can always be managed successfully. Patients with G3 tumors are more likely to have distant recurrences and should be closely monitored.

Background:The objective of this study is to evaluate the safety of fertility-sparing surgery (FSS) for early-stage epithelial ovarian cancer (EOC).Methods:A retrospective analysis was performed to identify patients treated for early-stage EOC and to compare the clinical outcomes of patients treated with FSS and radical surgery (RS).Results:A total of 1031 patients were treated at two Institutions, 242 with FSS (group A) and 789 with RS (group B). Median duration of follow-up was 11.9 years. At univariate analyses, FSS was associated with decreased risk of relapse (P=0.002) and of tumour-related death (P=0.001). Multivariate analysis did not confirm the independent positive role of FSS neither on relapse-free interval (RFI) nor on cancer-specific survival (CSS). Tumour grade was associated with shorter RFI (P<0.001) and shorter CSS (P=0.001). The type of treatment did not influence CSS or RFI in any grade group. We also found a significant association between low-grade tumours and younger age.Conclusions:Fertility-sparing surgery is an adequate treatment for patients with stage I EOC. The clinical outcome of patients with G3 tumours, which is confirmed to be the most important prognostic factor, is not determined by the type of treatment received.

Stage I epithelial ovarian cancer (EOC) represents about 10% of all EOCs and is characterized by good prognosis with fewer than 20% of patients relapsing. As it occurs less frequently than advanced-stage EOC, its molecular features have not been thoroughly investigated. We have demonstrated that in stage I EOC can predict patients' outcome. In the present study, we analyzed the expression of long non-coding RNAs (lncRNA) to enable potential definition of a non-coding transcriptional signature with prognostic relevance for stage I EOC. 202 snap-frozen stage I EOC tumor biopsies, 47 of which relapsed, were gathered together from three independent tumor tissue collections and subdivided into a training set ( = 73) and a validation set ( = 129). Median follow up was 9 years. LncRNAs' expression profiles were correlated in univariate and multivariate analysis with overall survival (OS) and progression-free survival (PFS). The expression of -, and was associated in univariate and multivariate analyses with relapse and poor outcome in both training and validation sets ( < 0.001). Using the expression profiles of -, and simultaneously, it was possible to stratify patients into high and low risk. The OS for high- and low-risk individuals are 36 and 123 months, respectively (OR, 15.55; 95% confidence interval, 3.81-63.36). We have identified a non-coding transcriptional signature predictor of survival and biomarker of relapse for stage I EOC. .

Improved cytoreductive surgery for advanced stage ovarian cancer (OC) represents a critical challenge in the treatment of the disease. Optimal debulking reaching no evidence of macroscopic disease is the primary surgical end point with a demonstrated survival advantage. Targeted molecule-based fluorescence imaging offers complete tumor resection down to the microscopic scale. We used a custom-built reflectance/ fluorescence imaging system with an orthotopic OC mouse model to both quantify tumor detectability and evaluate the effect of fluorescence image-guided surgery on postoperative survival. The contrast agent is an intraperitoneal injectable nanomolecular probe, composed of single-walled carbon nanotubes, coupled to an M13 bacteriophage carrying a modified peptide binding to the SPARC protein, an extracellular protein overexpressed in OC. The imaging system is capable of detecting a second near-infrared window fluorescence (1000−1700 nm) and can display real-time video imagery to guide intraoperative tumor debulking. We observed high microscopic tumor detection with a pixel-limited resolution of 200 μm. Moreover, in a survival-surgery orthotopic OC mouse model, we demonstrated an increased survival benefit for animals treated with fluorescence imageguided surgical resection compared to standard surgery.

Purpose: Epithelial ovarian cancer (EOC) is one of the most lethal gynecologic diseases, with survival rate virtually unchanged for the past 30 years. EOC comprises different histotypes with molecular and clinical heterogeneity, but up till now the present gold standard platinum-based treatment has been conducted without any patient stratification. The aim of the present study is to generate microRNA (miRNA) profiles characteristic of each stage I EOC histotype, to identify subtype-specific biomarkers to improve our understanding underlying the tumor mechanisms.Experimental Design: A collection of 257 snap-frozen stage I EOC tumor biopsies was gathered together from three tumor tissue collections and stratified into independent training (n ¼ 183) and validation sets (n ¼ 74). Microarray and quantitative real-time PCR (qRT-PCR) were used to generate and validate the histotype-specific markers. A novel dedicated resampling inferential strategy was developed and applied to identify the highest reproducible results. mRNA and miRNA profiles were integrated to identify novel regulatory circuits.Results: Robust miRNA markers for clear cell and mucinous histotypes were found. Specifically, the clear cell histotype is characterized by a five-fold (log scale) higher expression of miR-30a and miR-30a à , whereas mucinous histotype has five-fold (log scale) higher levels of miR-192/194. Furthermore, a mucinous-specific regulatory loop involving miR-192/194 cluster and a differential regulation of E2F3 in clear cell histotype were identified. Conclusions: Our findings showed that stage I EOC histotypes have their own characteristic miRNA expression and specific regulatory circuits. Clin Cancer Res; 19(15); 4114-23. Ó2013 AACR.

The understanding of basic molecular events in the tumorigenesis and chemoresistance of EOC together with discovery of potential biomarkers may be greatly enhanced through large-scale genomic studies. In order to maximize the impact of these technologies, however, extensive validation studies are required.

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