Advanced Serous Ovarian Carcinoma Research Articles

TP53 oncomorphic mutations predict resistance to platinum‑ and taxane‑based standard chemotherapy in patients diagnosed with advanced serous ovarian carcinoma.

Individual mutations in the tumor suppressor TP53 alter p53 protein function. Some mutations create a non-functional protein, whereas others confer oncogenic activity, which we term ‘oncomorphic’. Since mutations in TP53 occur in nearly all ovarian tumors, the objective of this study was to determine the relationship of oncomorphic TP53 mutations with patient outcomes in advanced serous ovarian cancer patients. Clinical and molecular data from 264 high-grade serous ovarian cancer patients uniformly treated with standard platinum- and taxane-based adjuvant chemotherapy were downloaded from The Cancer Genome Atlas (TCGA) portal. Additionally, patient samples were obtained from the University of Iowa and individual mutations were analyzed in ovarian cancer cell lines. Mutations in the TP53 were annotated and categorized as oncomorphic, loss of function (LOF), or unclassified. Associations between mutation types, chemoresistance, recurrence, and progression-free survival (PFS) were calculated. Oncomorphic TP53 mutations were present in 21.3% of ovarian cancers in the TCGA dataset. Patients with oncomorphic TP53 mutations demonstrated significantly worse PFS, a 60% higher risk of recurrence (HR=1.60, 95% confidence intervals 1.09, 2.33, p=0.015), and higher rates of platinum resistance (χ2 test p=0.0024) when compared with single nucleotide mutations not categorized as oncomorphic. Furthermore, tumors containing oncomorphic TP53 mutations displayed unique protein expression profiles, and some mutations conferred increased clonogenic capacity in ovarian cancer cell models. Our study reveals that oncomorphic TP53 mutations are associated with worse patient outcome. These data suggest that future studies should take into consideration the functional consequences of TP53 mutations when determining treatment options.

Proteomic Analysis of Matched Formalin-Fixed, Paraffin-Embedded Specimens in Patients with Advanced Serous Ovarian Carcinoma.

Objective: The biology of high grade serous ovarian carcinoma (HGSOC) is poorly understood. Little has been reported on intratumoral homogeneity or heterogeneity of primary HGSOC tumors and their metastases. We evaluated the global protein expression profiles of paired primary and metastatic HGSOC from formalin-fixed, paraffin-embedded (FFPE) tissue samples. Methods: After IRB approval, six patients with advanced HGSOC were identified with tumor in both ovaries at initial surgery. Laser capture microdissection (LCM) was used to extract tumor for protein digestion. Peptides were extracted and analyzed by reversed-phase liquid chromatography coupled to a linear ion trap mass spectrometer. Tandem mass spectra were searched against the UniProt human protein database. Differences in protein abundance between samples were assessed and analyzed by Ingenuity Pathway Analysis software. Immunohistochemistry (IHC) for select proteins from the original and an additional validation set of five patients was performed. Results: Unsupervised clustering of the abundance profiles placed the paired specimens adjacent to each other. IHC H-score analysis of the validation set revealed a strong correlation between paired samples for all proteins. For the similarly expressed proteins, the estimated correlation coefficients in two of three experimental samples and all validation samples were statistically significant (p < 0.05). The estimated correlation coefficients in the experimental sample proteins classified as differentially expressed were not statistically significant. Conclusion: A global proteomic screen of primary HGSOC tumors and their metastatic lesions identifies tumoral homogeneity and heterogeneity and provides preliminary insight into these protein profiles and the cellular pathways they constitute.

The time interval from surgery to start of chemotherapy significantly impacts prognosis in patients with advanced serous ovarian carcinoma — Analysis of patient data in the prospective OVCAD study

ObjectiveCytoreductive surgery and platinum-based systemic therapy constitute the standard treatment of patients with advanced ovarian cancer. The aim of the present study was to evaluate whether the time interval from surgery to start of chemotherapy has an impact on clinical outcome. MethodsData of 191 patients with advanced serous (FIGO III–IV) ovarian cancer from the prospective multicenter study OVCAD (OVarian CAncer Diagnosis) were analyzed. All patients underwent primary surgery followed by platinum-based chemotherapy. ResultsThe 25%, 50%, and 75% quartiles of intervals from surgery to start of chemotherapy were 22, 28, and 38days, respectively (range, 4–158days). Preoperative performance status (P<0.001), extent of surgery (P<0.001), and perioperative complications (P<0.001) correlated with intervals from surgery to initiation of chemotherapy. Timing of cytotoxic treatment [≤28days versus >28days; hazard ratio (HR) 1.73 (95% confidence interval 1.08–2.78), P=0.022], residual disease [HR 2.95 (95% confidence interval 1.87–4.67), P<0.001], and FIGO stage [HR 2.26 (95% confidence interval 1.41–3.64), P=0.001] were significant prognostic factors for overall survival in multivariate analysis. While the interval from surgery to start of chemotherapy did not possess prognostic significance in patients without postoperative residual disease (n=121), it significantly correlated with overall survival in patients with postoperative residual disease [n=70, HR 2.24 (95% confidence interval 1.08–4.66), P=0.031]. ConclusionOur findings suggest that delayed initiation of chemotherapy might compromise overall survival in patients with advanced serous ovarian cancer, especially when suboptimally debulked.

MiRNA expression pattern associated with prognosis in elderly patients with advanced OPSC and OCC

The long-term survival for elderly patients with advanced ovarian papillary serous carcinoma (OPSC) does not exceed 30%, and the incidence and prognosis rise continuously after menopause. The aim of this study was to identify the differences in key miRNAs and their potential regulators through miRNA microarray analysis, functional target prediction, and clinical outcome between the elderly patients with advanced OPSC and ovarian clear cell carcinoma (OCC) who all suffered poor prognosis, to identify the pathogenetic basis, and to improve the understanding of the molecular basis of advanced OPCS in elderly patients. Through microarray analysis, we found 52 unique miRNAs with significant fold‑change in expression levels, of which 9 were upregulated, whereas 43 were downregulated in OCC patients compared to elderly OPSC patients with advanced stage. Among these prediction miRNAs, miR-30a, miR-30e and miR-505 were found to have some common cancer-related targets. Lower expression of these three miRNAs of advanced OPSC in elderly patients, all associated with significantly poorer survival rate, strongly suggesting that they could be critical oncogenes and take important roles in OPSC etiology in elderly patients with advantaged stage. Functional analyses support the above hypothesis. Their targets, ATF3, STMN1 and MYC suggest that OPSC also has aggressive biological behavior when presented with advanced stage, and support the epidemiology results that incidence and mortality of advanced OPSC increases continuously. miR-30a, miR-30e and miR-505 may be important pathogenetic factors for OPSC in elderly patients with advanced stage. Age could be regarded as a continuous covariate in this process. This may improve the understanding of molecular underpinnings of advanced OPSC in elderly patients, and provide improved diagnostic, prognostic and therapeutic approaches.

Proteomic analysis of matched formalin-fixed, paraffin-embedded specimens in patients with advanced serous ovarian carcinoma

Objective: The biology of high-grade serous ovarian carcinoma (HGSOC) is poorly understood. Access to fresh-frozen primary tumors and matched metastatic sites is limited, but formalin-fixed, paraffin-embedded (FFPE) tissues are more readily available. Proteomic analysis of HGSOC thus far has focused on the identification of serum biomarkers, while little data have been reported regarding heterogeneity of primary ovarian tumors and their metastases. In this pilot study, our goal was to evaluate the protein expression profiles of paired primary and metastatic tumor from FFPE ovarian samples.

Increased CD70 expression is associated with clinical resistance to cisplatin-based chemotherapy and poor survival in advanced ovarian carcinomas

BackgroundCD70 has been regarded as a novel potential therapeutic target for multiple cancers. In this study, we characterized the expression of the CD70 protein in ovarian carcinomas and assessed its clinical-pathological prognostic value.Materials and methodsThe expression of CD70 in advanced ovarian cancer specimens was assessed by immunohistochemistry. Our results indicated that 16 out of 92 (17.4%) advanced ovarian serous carcinoma tumors showed a high level of CD70 expression. Furthermore, CD70 overexpression was significantly associated with cisplatin-based chemotherapy responses. The high CD70 expression subgroup demonstrated a higher incidence of chemotherapy resistance than the low CD70 subgroup (68.8% versus 25.0%, P = 0.001). Furthermore, univariate analysis conducted on subsets of ovarian carcinoma indicated that high CD70 expression was also associated with decreased survival rates; retained significance was observed on multivariate analysis.ConclusionGiven the elevated expression of CD70 and its relationship with drug resistance and poor prognosis, our findings suggest that a minor proportion of ovarian carcinomas with CD70 overexpression might be a candidate for the emerging anti-CD70 antibody drug conjugates or therapeutic anti-CD70 antibodies.

Relationship of microRNA expression profiles and recurrence in advanced serous ovarian carcinoma.

5557 Background: Most patients with epithelial ovarian cancer eventually succumb to chemo-resistant disease. Although microRNAs have been recognized as important regulators of gene expression, little is known about microRNA expression profiles in recurrent serous ovarian carcinoma. We assessed the microRNA expression profiles which contribute to recurrence in advanced serous ovarian carcinoma. Methods: Eight pairs of primary and recurrent tumor samples from 8 patients with advanced serous ovarian carcinoma and 4 normal ovarian samples from patients treated for benign uterine disease between May 2006 and Dec 2012 were examined using miRNA microarray. microRNA profiling were validated using real-time reverse transcription-polymerase chain reaction (RT-PCR). Results: Alterations of microRNA expression profiles in primary and recurrent tumor samples have similar patterns when compared with normal ovarian tissues. Among 31 up-regulated microRNAs more than 4-fold in primary tumors, 27 microRNAs were also significantly up-regulated in recurrent tumor samples. Likewise, Among 35 down-regulated microRNAs more than 4-fold in primary tumors, 34 microRNAs were also significantly down-regulated in recurrent tumor samples. Comparing to primary tumor, we found 60 microRNAs which were significantly up-regulated, including miR-630, 370, and 575, and 52 microRNAs which were significantly down-regulated, including miR-509-3p, 514a-3p, and 506-3p in recurrent serous ovarian carcinoma. Conclusions: Our results indicate that dysregulation of microRNAs may play a role in recurrence of serous ovarian carcinoma.

Abstract 3158: Transcription factor SOX11 decreases viability in ovarian carcinoma cells.

Abstract Objective: The Cancer Genome Atlas (TCGA) evaluated nearly 500 advanced serous ovarian carcinomas and identified four gene expression subclasses. The transcription factor SOX11 was markedly overexpressed in the proliferative subtype and associated with phosphorylation of other cell cycle related proteins including CHEK2, WWTR1, and EIF4EBP1. We tested the hypothesis that over-expression of SOX11 will decrease proliferation of ovarian cancer cells through transcriptional repression. Methods: SOX11 was overexpressed via lipofectamine transfection in the TP53 wild-type ovarian cancer cell line SKOV3 and the TP53 mutated ovarian cancer cell line OVCAR3. Cell proliferation was assessed 48 hours after transfection using the VisionBlue fluorescence-based viability assay. Cell cycle analysis was performed utilizing a propidium iodide (PI) assay followed by fluorescence-activated cell sorting (FACS). Finally migration of SOX11-transfected cells was analyzed in comparison to mock-transfected controls via monolayer scratch assay. Results: Successful overexpression of the SOX11 protein was confirmed using GFP fluoroscopy and western blot 24 and 48 hours following transfection. Cell viability was reduced by 14-63% at 48 hours in SOX11-transfected SKOV3 cells compared to mock controls (P = 0.01) in a dose dependent fashion. Cell cycle was unaffected by SOX11 overexpression. Finally, the monolayer scratch assay demonstrated that cells overexpressing SOX11 migrated more slowly than mock controls (median velocity 3.92 vs. 6.19 um/hr, P = 0.001). Data from OVCAR3 cells are currently being analyzed and will be presented. Conclusions: Overexpression of SOX11 resulted in decreased cell viability without affecting cell cycle. Further studies will assess the mechanism of this decreased viability which may involve diversion toward an apoptotic pathway when SOX11 is overexpressed or regulation by transcription repressors such as WWTR1. SOX11 suppression has been shown in lymphoma to be associated with more aggressive tumors through mechanisms associated with lysophosphatidic acid growth regulation, offering mechanistic associations with ovarian cancer. Ongoing work will determine the relationship between SOX11 and TP53 mutation frequently found in high-grade serous carcinoma. These studies will help to explain the differential outcomes seen across high-grade serous ovarian carcinoma. Citation Format: Caryn M. St. Clair, Stephanie L. Wethington, Maria Bisogna, Fanny Dao, Petar Jelinic, Douglas A. Levine. Transcription factor SOX11 decreases viability in ovarian carcinoma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3158. doi:10.1158/1538-7445.AM2013-3158

Lung Resistance-Related Protein (LRP) Expression in Malignant Ascitic Cells as a Prognostic Marker for Advanced Ovarian Serous Carcinoma

Ovarian serous carcinoma is an aggressive cancer that often presents with metastatic disease. Although primary tumor and established metastatic foci in the omentum are generally compared to identify proteins involved in drug resistance, we investigated a potential bridge, the malignant cells from ascites, as facilitator of drug resistance and recurrence. We evaluated the expression of drug resistance markers P-glycoprotein (P-gp), canalicular multispecific organic anion transporter (MRP2), and lung resistance-related protein (LRP) in malignant cells from ascites and matched omental metastasis from 25 patients with advanced-stage ovarian serous carcinoma who were chemotherapeutic naïve and undergoing initial cytoreductive surgery. Cell viability in vitro, patient response to chemotherapy, and patient survival were correlated with these biomarkers. Of the 25 patients evaluated for a correlation of LRP to 1-year recurrence, we correctly predicted the 1-year recurrence of 24 patients based solely on the presence of LRP in ascitic tumor cells (p=0.01). P-gp and MRP2 were not expressed in malignant cells of ascites or omental metastases. Malignant cells from ascites had higher expression of LRP and were found to be more resistant to carboplatin treatment than cells from omental metastasis (p=0.00375) by in vitro assay. LRP expression in the malignant cells of ascites correlated with carboplatin resistance (p=0.001) by in vitro assay and recurrence at 1 year (p=0.0125). LRP expression in malignant cells of ascites is a promising marker to predict response to first-line chemotherapy in patients with advanced ovarian serous carcinoma.

Epigenetic silencing of BLU through interfering apoptosis results in chemoresistance and poor prognosis of ovarian serous carcinoma patients

Epithelial ovarian carcinoma is usually present at the advanced stage, during which the patients generally have poor prognosis. Our study aimed to evaluate the correlation of gene methylation and the clinical outcome of patients with advanced-stage, high-grade ovarian serous carcinoma. The methylation status of eight candidate genes was first evaluated by methylation-specific PCR and capillary electrophoresis to select three potential genes including DAPK, CDH1, and BLU (ZMYND10) from the exercise group of 40 patients. The methylation status of these three genes was further investigated in the validation group consisting of 136 patients. Patients with methylated BLU had significantly shorter progression-free survival (PFS; hazard ratio (HR) 1.48, 95% CI 1.01-2.56, P=0.013) and overall survival (OS; HR 1.83, 95% CI 1.07-3.11, P=0.027) in the multivariate analysis. Methylation of BLU was also an independent risk factor for 58 patients undergoing optimal debulking surgery for PFS (HR 2.37, 95% CI 1.03-5.42, P=0.043) and OS (HR 3.96, 95% CI 1.45-10.81, P=0.007) in the multivariate analysis. A possible mechanism of BLU in chemoresistance was investigated in ovarian cancer cell lines by in vitro apoptotic assays. In vitro studies have shown that BLU could upregulate the expression of BAX and enhance the effect of paclitaxel-induced apoptosis in ovarian cancer cells. Our study suggested that methylation of BLU could be a potential prognostic biomarker for advanced ovarian serous carcinoma.

Validated gene targets associated with curatively treated advanced serous ovarian carcinoma

ObjectivesHigh-grade serous ovarian cancer (HGSOC) mostly presents at an advanced stage and has a low overall survival rate. However, a subgroup of patients are seemingly cured after standard initial therapy. We hypothesize that the molecular profiles of these patients vary from long-term survivors who recur. MethodsPatients with advanced HGSOC who underwent primary cytoreductive surgery and platinum-based chemotherapy were identified from The Cancer Genome Atlas (TCGA) and institutional (MSKCC) samples. A curative-intent group was defined by recurrence-free survival of >5years. A long-term recurrent group was composed of patients who recurred but survived >5years. RNA was hybridized to Affymetrix U133A transcription microarrays. The NanoString nCounter gene expression system was used for validation in an independent patient population. ResultsIn 30 curative and 84 recurrent patients, class comparison identified twice as many differentially expressed probes between the groups than expected by chance alone. TCGA and MSKCC data sets had 19 overlapping genes. Pathway analyses identified over-represented networks that included nuclear factor kappa B (NFkB) transcription and extracellular signal-regulated kinase (ERK) signaling. External validation was performed in an independent population of 28 curative and 38 recurrent patients. Three genes (CYP4B1, CEPT1, CHMP4A) in common between our original data sets remained differentially expressed in the external validation data. ConclusionsThere are distinct transcriptional elements in HGSOC from patients likely to be cured by standard primary therapy. Three genes have withstood rigorous validation and are plausible targets for further study, which may provide insight into molecular features associated with long-term survival and chemotherapy resistance mechanisms.

Romiplostim overcomes refractory secondary immune thrombocytopenia in a patient affected by serous ovarian carcinoma

Immune thrombocytopenia (ITP) is an autoimmune disorder that occasionally arises with neoplasms. Although often sensitive to first-line treatment, a refractory thrombocytopenia may lead to a difficult management of the patient. A patient with primary ITP who successfully underwent surgery and chemotherapy with immunoglobulins and dexamethasone for ovarian cancer has recently been reported. We report on a 71-year-old woman who developed refractory secondary ITP concomitant with an advanced serous ovarian carcinoma. The ITP responded only to the thrombopoietin receptor agonist romiplostim with an uncommon threshold effect, enabling both palliative surgery and histological diagnosis. Although thrombopoietin receptor agonists might be useful in some circumstances, their safety and efficacy for cancer patients must still be determined. Well-designed clinical trials are urgently needed to resolve this issue.

The Significance of p53 Isoform Expression in Serous Ovarian Cancer

Epithelial ovarian cancer still carries a high mortality rate and remains the leading cause of gynecologic cancer death in the USA, despite decades of research. Hence, there is considerable interest in developing biomarkers that could be used to stratify patients for subsequent treatment. Mutation of the p53 tumor suppressor gene occurs very frequently (∼96%) in high-grade serous ovarian cancer. However, loss of p53 has not proven to be a reliable prognostic marker. Recent evidence indicates that the truncated p53 protein isoforms can regulate activated p53 and thus may play a role in tumorigenesis. In the article by Hofstetter et al., the authors examined the relationship between the expression of two p53 isoforms (Δ133p53 and Δ40p53) and prognosis in patients with serous ovarian cancer. Their findings indicate that Δ133p53 constitutes an independent prognostic marker for improved recurrence-free and overall survival. Intriguingly, this relationship was observed in patients whose tumors expressed a mutant p53, suggesting that Δ133p53 might suppress the actions of mutant p53. The mutational status of p53 alone did not have prognostic significance. These studies suggest that mutant p53 activity may be counteracted by Δ133p53, which leads to a more favorable prognosis in advanced serous ovarian carcinomas. Novel therapeutic approaches could be built upon these findings.

Validated gene targets associated with curatively treated advanced serous ovarian carcinoma

Objective: Ovarian cancer mostly presents at an advanced stage and has a low overall survival rate. However, there is a subgroup of patients who present with advanced-stage disease, receive standard initial therapy, and are seemingly cured. We hypothesize that molecular profiles of survivors who are apparently cured by initial treatment will be different from survivors who recurred.

Treatment-Related Protein Biomarker Expression Differs between Primary and Recurrent Ovarian Carcinomas

The molecular characteristics of recurrent ovarian cancers following chemotherapy treatment have been poorly characterized. Such knowledge could impact salvage therapy selection. Since 2008, we have profiled 168 patients' ovarian cancers to determine the expression of proteins that may predict chemotherapy response or are targets for drugs that are in clinical trials for ovarian cancer treatment. Expression of epidermal growth factor receptor (EGFR), HER2, VEGF, ER, c-Met, IGF1R, Ki67, COX2, PGP/MDR1, BCRP, MRP1, excision repair complementation group 1 (ERCC1), MGMT, TS, RRM1, TOPO1, TOP2A, and SPARC was measured by immunohistochemical analyses at Clinical Laboratory Improvement Amendments-certified laboratories. Our univariate analysis of 56 primary and 50 recurrent tumors from patients with advanced stage ovarian serous carcinoma revealed that PGP and ERCC1 were significantly upregulated in recurrent lesions (P < 0.05). To determine whether these or any of the other markers were differentially expressed in specimens obtained from the same individual at diagnosis and at recurrence, we analyzed 43 matched tumor specimens from 19 advanced stage ovarian carcinoma patients. We confirmed the expression differences in PGP and ERCC1 that were observed in the cohort analysis but discovered that the expression levels of BCRP, RRM1, and COX2 were also discordant in more than 40% of the matched tumor specimens. These results may have implications both for the use of biomarkers in therapy selection as well as for their discovery and validation. Expression of these and other candidate response biomarkers must be evaluated in much larger studies and, if confirmed, support the need for profiling of recurrent tumor specimens in future clinical trials.

Microarray-based oncogenic pathway profiling in advanced serous papillary ovarian carcinoma.

IntroductionThe identification of specific targets for treatment of ovarian cancer patients remains a challenge. The objective of this study is the analysis of oncogenic pathways in ovarian cancer and their relation with clinical outcome.MethodologyA meta-analysis of 6 gene expression datasets was done for oncogenic pathway activation scores: AKT, β-Catenin, BRCA, E2F1, EGFR, ER, HER2, INFα, INFγ, MYC, p53, p63, PI3K, PR, RAS, SRC, STAT3, TNFα, and TGFβ and VEGF-A. Advanced serous papillary tumours from uniformly treated patients were selected (N = 464) to find differences independent from stage-, histology- and treatment biases. Survival and correlations with documented prognostic signatures (wound healing response signature WHR/genomic grade index GGI/invasiveness gene signature IGS) were analysed.ResultsThe GGI, WHR, IGS score were unexpectedly increased in chemosensitive versus chemoresistant patients. PR and RAS activation score were associated with survival outcome (p = 0.002;p = 0.004). Increased activations of β-Catenin (p = 0.0009), E2F1 (p = 0.005), PI3K (p = 0.003) and p63 (p = 0.05) were associated with more favourable clinical outcome and were consistently correlated with three prognostic gene signatures.ConclusionsOncogenic pathway profiling of advanced serous ovarian tumours revealed that increased β-Catenin, E2F1, p63, PI3K, PR and RAS –pathway activation scores were significantly associated with favourable clinical outcome. WHR, GGI and IGS scores were unexpectedly increased in chemosensitive tumours. Earlier studies have shown that WHR, GGI and IGS are strongly associated with proliferation and that high-proliferative ovarian tumours are more chemosensitive. These findings may indicate opposite confounding of prognostic versus predictive factors when studying biomarkers in epithelial ovarian cancer.

BMP-4 expression has prognostic significance in advanced serous ovarian carcinoma and is affected by cisplatin in OVCAR-3 cells

Several angiogenesis-promoting factors have prognostic significance in ovarian cancer. The objective of this study was to evaluate whether traditional chemotherapy affects angiogenesis-related factors in ovarian carcinoma and to assess the clinical significance of these effects. To screen for angiogenesis-related factors of possible relevance, OVCAR-3 and A2780 ovarian cancer cells were treated with IC(50) doses of cisplatin (CDDP) or docetaxel, or with bevacizumab, and mRNA expression of several angiogenesis-related factors was analyzed. Thrombospondin-1 (TSP-1), bone morphogenetic protein-4 (BMP-4), endothelin-1, and placental growth factor-2 were statistically significantly induced by CDDP. At protein level, CDDP also induced hypoxia-inducible factor-1α but not vascular endothelial growth factor. In carcinoma samples taken before and after platinum-based neoadjuvant chemotherapy from 28 patients with advanced, high-grade serous ovarian carcinoma, CD105 and factors most induced by CDDP (TSP-1 and BMP-4) were analyzed by immunohistochemistry. Strong expression of BMP-4 before chemotherapy was an independent prognostic factor of longer progression-free time (p = 0.002) and overall survival (p = 0.02), but it was not associated with neovascularization (as evaluated by CD105). However, changes in BMP-4 expression in samples analyzed before and after chemotherapy (observed in 22/28 patients) were not associated with prognosis. TSP-1 expression was not associated with clinical parameters. Our results indicate that in serous ovarian carcinoma, BMP-4 has prognostic significance, which is not angiogenesis-related. We also show that CDDP induces several angiogenesis-related growth factors in vitro and future studies are warranted to clarify the clinical significance of this phenomenon.

Does operative start time impact the frequency of complete gross resection in patients undergoing primary cytoreduction for advanced serous ovarian carcinoma?

Does operative start time impact the frequency of complete gross resection in patients undergoing primary cytoreduction for advanced serous ovarian carcinoma?

Abstract 398: Interleukin 6 may predict chemoresistant ovarian cancer

Abstract Interleukin 6 (IL-6) has been hypothesized to facilitate the growth and progression of some malignancies by increasing angiogenesis. The aim of this study was to evaluate ovarian ascites from chemotherapy-naïve ovarian cancer patients and determine whether cytokines including IL-6 could predict resistance. After IRB approval, patient ascites and metastatic implants were collected. The metastatic implants were evaluated for platinum sensitivity by treatment with 50 uM carboplatin for 48 hours and then cell viability was analyzed. The cells were removed by centrifugation from the ascites fluid and expression of IL-6, IL-1a, IL-1ra, IL-8, VEGF, and RANTES was evaluated in the fluid and lysed cells separately using a Millipore Custom Magnetic Bead Kit (Millipore, Billerica, MA) on a Bio-Plex Cytokine Assay (Bio-Rad Laboratories, Hercules, CA). Twelve patients with advanced stage ovarian papillary serous carcinoma undergoing primary cytoreductive surgery had ascites samples which were adequate for analysis. Six patients were platinum sensitive and 6 patients were platinum resistant. IL-6 levels in the acellular fluid correlated with chemoresistance (P = 0.05). IL-1a and IL-1ra levels tended to be associated with chemoresistance (P = 0.22; P = 0.1) while IL-8 and VEGF levels tended to be associated with chemosensitivity (P = 0.23; P = 0.16). RANTES showed no association with either chemoresistance or chemosensitivity. Levels of cytokines extracted from the cells were low and did not impact the results of analysis of the cytokines. We conclude that levels of IL-6 in ascites may indicate platinum resistance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 398. doi:10.1158/1538-7445.AM2011-398

Molecular profiling of patients with curatively treated advanced serous ovarian carcinoma from The Cancer Genome Atlas

Molecular profiling of patients with curatively treated advanced serous ovarian carcinoma from The Cancer Genome Atlas