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Understanding predictors of successful ageing is essential to policy development promoting quality-of-life of an ageing population. Initial models precluded successful ageing in the presence of chronic disease/functional disability; however, this is discrepant with self-reported successful ageing. Indicators of social, psychological and physical health in 1,735 people aged 65–74, living in Canada, Columbia, Brazil or Albania, were analysed in the International Mobility in Ageing Study. Multiple logistic regression analysis was performed to estimate the change in self-rated successful ageing in relation to physical health, depression, social connectedness, resilience and site, while controlling for age, gender and income sufficiency. Sixty-five per cent of participants self-rated as ageing successfully; however, this was significantly different across sites (p < 0.0005, range 17–85%) and gender (p = 0.019). Using objective measures, 6 per cent were classified as ‘successful’, with significant variability amongst sites (p < 0.0005, range 0–12%). Subjective successful ageing was associated with fewer (not absence of) chronic diseases, absence of depression and less dysfunction in activities of daily living, but not with objective measures of physical dysfunction. Social connectedness and resilience also aligned with self-rated successful ageing. Traditional definitions of objective successful ageing are likely too restrictive, and thus, do not approximate self-rated successful ageing. International differences suggest that site could be a surrogate for variables other than physical/mental health and social engagement.

Objective To investigate the ability of preoperative CA125 and post-surgical CA125 changes to predict outcomes among patients with high-grade serous ovarian cancer (HGSC). Methods The present retrospective cohort study included patients with HGSC who underwent surgery between January 1, 2003, and December 31, 2011 at Princess Margaret Cancer Center, Toronto, ON, Canada. CA125 was measured at diagnosis and following surgery, and the CA125 ratio was calculated (preoperative CA125/postoperative CA125). Optimal CA125 cutoff levels were identified using the point with the most significant log-rank-test result. Univariate and multivariate analyses with Cox proportional hazard modeling was used to study overall survival. Results Among 212 patients, an optimal baseline CA125 cutoff value of 174 U/mL and a seven-fold decrease in CA125 after surgery were positive prognostic indicators. A 10-fold increase in baseline CA125 was associated with decreased overall survival (univariate hazard ratio 1.55, 95% confidence interval [CI] 1.17–2.06; P=0.002; multivariate hazard ratio 1.72, 95% CI 1.21–2.44; P=0.002). An increase in the CA125 ratio (log10[preoperative CA125/postoperative CA125]) was associated with improved overall survival (univariate hazard ratio 0.63, 95% CI 0.43–0.90; P=0.012; multivariate hazard ratio 0.41, 95% CI 0.24–0.70, P

Epithelial ovarian cancer is the most common cause of death from gynecologic malignancy.1 High-grade serous ovarian cancer (HGSC) is the most common type of epithelial ovarian cancer, representing 70% of all diagnosed tumours.2 Most ovarian cancers (70%) are diagnosed at an advanced stage of disease (Stage III/IV), and 80%–90% of these advanced-stage tumours are HGSC.3 As such, the 5-year overall survival rate for women with HGSC is approximately 44%. The standard of care treatment for HGSC has essentially remained the same for the past 2 decades and includes a combination of surgical cytoreduction and platinum-/taxane-based adjuvant chemotherapy.4,5 However, despite aggressive surgery and chemotherapy, cure is rare for the majority of women with HGSC. Survival in these patients largely depends on the tumour sensitivity to platinum-based chemotherapy6,7 and the degree of surgical cytoreduction.8,9 Even extensive surgeries leaving more than 1 cm of residual tumour have limited impact on survival.10–12 Since the original publication by Griffiths,9 which suggested an association between the amount of residual disease and survival, the definition of “optimal” cytoreduction has been shifting from an initial definition of no single residual lesion measuring less than 2 cm in diameter to a definition of less than 1 cm and, most recently, to a definition of no macroscopic disease.13–15 As optimal surgical cytoreduction is one of the strongest predictors of outcome for patients with HGSC, many studies have investigated the use of neoadjuvant chemotherapy as an alternative treatment strategy to reduce tumour burden before surgery.16 There are several putative advantages of the neoadjuvant treatment strategy, including less extensive surgery, reduced morbidity and increased optimal cytoreduction. Furthermore, it currently provides the only means to identify patients with platinum-resistant disease at presentation.17 Many studies suggest equivalent survival in patients receiving adjuvant versus neoadjuvant chemotherapy.18–28 Notably, Vergote and colleagues20 reported the only phase III randomized controlled trial in which patients with advanced-stage HGSC were treated with either primary surgery and adjuvant platinum-based chemotherapy (PCS group) or neoadjuvant platinum-based chemotherapy followed by interval cytoreductive surgery and additional adjuvant chemotherapy (NAC group). Although patients in the NAC group had higher rates of optimal cytoreduction and fewer perioperative complications, this did not translate into improved survival. This trial was criticized by many for poor progression-free and overall survival rates in both study arms.29–31 Importantly, several studies addressing the use of primary surgery versus neoadjuvant chemotherapy indicated that patients in the NAC group have inferior overall survival than patients in the PCS group.32–34 Bristow and Chi16 conducted a meta-analysis that suggested the number of neoadjuvant chemotherapy cycles before surgery was inversely proportional to the median overall survival. In addition, these authors demonstrated that although the difference in survival between the NAC and PCS groups did not reach statistical significance in previous studies, survival was often reduced by up to half in the NAC group.19 Hence, controversy remains about the use of neoadjuvant chemotherapy as a first-line treatment in patients with HGSC. Surveys of members of the Society of Gynecolologic Oncology35 and the European Society of Gynecologic Oncology36 suggest that 18% and 70% of gynecologic oncologists, respectively, routinely recommend neoadjuvant chemotherapy to their patients. Furthermore, the appropriate number of neoadjuvant chemotherapy cycles that should be administered before interval cytoreductive surgery is subject to debate. Hence, a deeper understanding of the effect of the treatment strategy, post-treatment tumour biology and survival outcomes are required. In this study, we examine the progression-free and overall survival of patients in the NAC group as compared with patients in the PCS group. The objective of this work was to study surgical factors, including the timing of surgery, in relation to the number of preoperative neoadjuvant chemotherapy cycles and the rate of optimal cytoreduction in the NAC and PCS groups. We aimed to analyze the impact of these factors on survival in women with HGSC.

High-grade serous ovarian cancer (HGSC) is the leading cause of morbidity and mortality from gynecologic malignant tumors. Overall survival remains low because of the nearly ubiquitous emergence of platinum resistance and the paucity of effective next-line treatments. Current cell culture–based models show limited similarity to HGSC and are therefore unreliable predictive models for preclinical evaluation of investigational drugs. This deficiency could help explain the low overall rate of successful drug development and the decades of largely unchanged approaches to HGSC treatment. We used gene expression, copy number variation, and exome sequencing analyses to credential HGSC patient–derived xenografts (PDXs) as effective preclinical models that recapitulate the features of human HGSC. Mice bearing PDXs were also treated with standard-of-care carboplatin therapy. PDXs showed similar sensitivity to carboplatin as the patient's tumor at the time of sampling. PDXs also recapitulated the diversity of genomic alterations (copy number variation and mutation profiles) previously described in large data sets that profiled HGSC. Furthermore, mRNA profiling showed that the PDXs represent all HGSC subtypes with the exception of the immunoreactive group. Credentialing of PDX models of HGSC should aid progress in HGSC research by providing improved preclinical models of HGSC that can be used to test novel targets and more accurately evaluate their likelihood of success.

Ovarian cancer is the leading cause of morbidity/mortality from gynecologic malignancy. Early detection of disease is difficult due to the propensity for ovarian cancer to disseminate throughout the peritoneum. Currently, there is no single accurate test to detect primary or recurrent ovarian cancer. We report a novel clinical strategy using PPF: a multimodal, PET and optical, folate receptor (FR)-targeted agent for ovarian cancer imaging. The capabilities of PPF were evaluated in primary human ovarian cancer cells, in vivo xenografts derived from primary cells and ex vivo patient omemtum, as the heterogeneity and phenotype displayed by patients is retained. Primary cells uptake PPF in a FR-dependent manner demonstrating approximately a 5- to 25-fold increase in fluorescence. By both PET and fluorescence imaging, PPF specifically delineated FR-positive, ovarian cancer xenografts, with similar tumor-to-background ratios of 8.91±0.91 and 7.94±3.94, and micro-metastatic studding (

SummaryThe pentaspan membrane glycoprotein CD133 marks lineage-specific cancer progenitor cells and is associated with poor prognosis in a number of tumor types. Despite its utility as a cancer progenitor cell marker, CD133 protein regulation and molecular function remain poorly understood. We find that the deacetylase HDAC6 physically associates with CD133 to negatively regulate CD133 trafficking down the endosomal-lysosomal pathway for degradation. We further demonstrate that CD133, HDAC6, and the central molecule of the canonical Wnt signaling pathway, β-catenin, can physically associate as a ternary complex. This association stabilizes β-catenin via HDAC6 deacetylase activity, which leads to activation of β-catenin signaling targets. Downregulation of either CD133 or HDAC6 results in increased β-catenin acetylation and degradation, which correlates with decreased proliferation in vitro and tumor xenograft growth in vivo. Given that CD133 marks progenitor cells in a wide range of cancers, targeting CD133 may be a means to treat multiple cancer types.

Cell surface proteins have a wide range of biological functions, and are often used as lineage-specific markers. Antibodies that recognize cell surface antigens are widely used as research tools, diagnostic markers, and even therapeutic agents. The ability to obtain broad cell surface protein profiles would thus be of great value in a wide range of fields. There are however currently few available methods for high-throughput analysis of large numbers of cell surface proteins. We describe here a high-throughput flow cytometry (HT-FC) platform for rapid analysis of 363 cell surface antigens. Here we demonstrate that HT-FC provides reproducible results, and use the platform to identify cell surface antigens that are influenced by common cell preparation methods. We show that multiple populations within complex samples such as primary tumors can be simultaneously analyzed by co-staining of cells with lineage-specific antibodies, allowing unprecedented depth of analysis of heterogeneous cell populations. Furthermore, standard informatics methods can be used to visualize, cluster and downsample HT-FC data to reveal novel signatures and biomarkers. We show that the cell surface profile provides sufficient molecular information to classify samples from different cancers and tissue types into biologically relevant clusters using unsupervised hierarchical clustering. Finally, we describe the identification of a candidate lineage marker and its subsequent validation. In summary, HT-FC combines the advantages of a high-throughput screen with a detection method that is sensitive, quantitative, highly reproducible, and allows in-depth analysis of heterogeneous samples. The use of commercially available antibodies means that high quality reagents are immediately available for follow-up studies. HT-FC has a wide range of applications, including biomarker discovery, molecular classification of cancers, or identification of novel lineage specific or stem cell markers.

The cancer stem cell (CSC) model proposes that tumors have a hierarchical organization in which only some cells indefinitely self-renew and thereby sustain tumor growth. In addition, the CSC model requires that tumor-initiating cells (TICs) be prospectively isolatable on the basis of their phenotype. Previous studies have suggested that serous ovarian cancer (SOC) conforms to the CSC model, but these used arguably nonfidelitous immortalized cell lines, cultured primary cells, or passaged xenografts as the source of tumor cells. We developed a robust assay for quantifying TICs from primary SOC. Using this assay, we find that TICs are rare when assayed in either NOD/SCID or NOD/SCID/IL2Rγ −/− (NSG) mice. TIC frequency (TICf) varies substantially between patients, although it is similar in primary ovarian masses and omental metastases, suggesting that TICf is an intrinsic property of ovarian tumors. CD133 marks all TICs from several primary SOC cases. However, in other cases, substantial TIC activity is found in both the CD133 + and CD133 − fractions, whereas still other cases have exclusively CD133 − TICs. Furthermore, the TIC phenotype can change in xenografts: primary tumors in which all TICs are CD133 + can give rise to xenografts that contain substantial numbers of CD133 − TICs. Our results highlight the need for quantitative rigor in the evaluation of TICs and for caution when using passaged xenografts for such studies. Furthermore, although our data suggest that SOC conforms to the CSC hypothesis, the heterogeneity of the TIC phenotype may complicate its clinical application.

Serum prostate specific antigen screening has increased the number of prostate biopsies performed increasing the number of patients with high grade prostatic intraepithelial neoplasia. The criteria for re-biopsy are not standardized but may be refined by the identification of novel biomarkers demonstrating prognostic significance. Alpha-methylacyl-CoA racemase is a robust marker of prostate cancer and is expressed in a subset of high grade prostatic intraepithelial neoplasia. This study evaluates the prognostic significance of alpha-methylacyl-coA racemase positive high grade prostatic intraepithelial neoplasia glands in prostate biopsies.Immunohistochemical staining with alpha-methylacyl-coA racemase and p63 was examined in a selected group of 62 patients with a diagnosis of high grade prostatic intraepithelial neoplasia on initial prostate biopsy, of which on repeat biopsy 32 had no carcinoma and 30 had prostate cancer. There was no significant difference in age, number of cores sampled or prostate specific antigen history between the 2 outcome groups (ANOVA p0.9). High grade prostatic intraepithelial neoplasia glands in each case were evaluated for alpha-methylacyl-coA racemase and p63.Reactivity for alpha-methylacyl-coA racemase was found in 27 of the 62 cases examined. Fisher's exact analysis revealed that patients with at least 1 alpha-methylacyl-coA racemase positive high grade prostatic intraepithelial neoplasia gland were 5.2 times more likely to have a subsequent diagnosis of prostate cancer on repeat biopsy than those without any alpha-methylacyl-coA racemase positive high grade prostatic intraepithelial neoplasia glands (p = 0.0044). No correlation was found between alpha-methylacyl-coA racemase positivity and any other clinical variable.This is the first study to our knowledge to illustrate that alpha-methylacyl-coA racemase reactivity in high grade prostatic intraepithelial neoplasia may be useful to refine re-biopsy criteria and assist in clinical management decisions.

High grade serous ovarian carcinoma has been shown to be a highly heterogeneous disease. In vivo studies demonstrate that the tumor initiating frequency (TIF) varies substantially from case to case. Nonetheless, the tumor initiating subset remains a rare population within the epithelial compartment and can be enriched using the cell surface marker CD133 (Stewart et al., PNAS, 2011). The tumor microenvironment may play a role in supporting and maintaining tumor initiating cells (TIC) through direct and/ or indirect cross talk. The contribution of the mesenchymal component of the microenvironment may prove to be essential in providing such support as has been previously shown in studies on breast and prostate cancers. We hypothesize that cancer associated fibroblasts (CAFs) serve as a niche that supports and maintains the tumorigenic potential of TICs in SOC. We have derived and established CAF lines from bulk primary tumors and characterized their phenotype through immunostaining. Those lines stained positive for mesenchymal markers (Vimentin and Alpha-SMA), and stained negative for the epithelial marker Cytokertain. A profile of surface markers expressed on the surface of these CAF lines was then generated by running a flow cytometry-based high throughput screen (HTS) for 370 known cell surface proteins. Those markers are being validated for their specificity by immunostaining, FACS, qPCR, and in vivo work. Preliminary data obtained through immunoflourescnce and FACS support the specificity of our candidate stromal marker CD90. Furthermore, FACS data show that CD90 is expressed more brightly on fibroblasts than on epithelial cells (EpCAM+) in bulk SOC cases. Consequently, CD90 has been selected for sorting stromal cells for additional validation. Quantitative PCR analysis of CD90+EpCAM- sorted populations further validates their over-expression of mesenchymal genes when compared to CD90-EpCAM+ sorted populations. Moreover, functional validation of the influence of fibroblasts on the growth of tumor cells is currently being investigated through co-injection and co-culture assays. Preliminary data show that the presence of fibroblasts better supports the growth of epithelial colonies in culture than when compared to other conditions. Interplay between the niche and a specific subset of epithelial cells may promote those cells to become more tumorigenic. Such an interaction may be dependent on direct physical contact and/or indirect cross talk. Ultimately, we aim on understanding the mechanisms that govern these interactions. Citation Format: Ali Hussain, Jocelyn Stewart, Elzbieta Hyatt, Benjamin Neel, Laurie Ailles. The role of stromal cells in supporting tumor-initiating cells in serous ovarian carcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B12.

Serous ovarian cancer (SOC) is the leading cause of morbidity/mortality from gynecologic malignancy. Current therapies significantly increase survival, yet 70-90% of SOC patients recur within five years and die of their disease. The cancer stem cell (CSC) hypothesis holds that only some tumor cells have the potential to initiate and maintain tumors. Moreover, CSC might be resistant to many therapeutic agents that are effective against bulk tumor cells, which could contribute to treatment failure. We have established a large collection of primary human SOC samples and developed a robust, quantitative assay for SOC tumor-initiating cells (TIC). Using this assay, we found that TIC from primary SOC can be identified based on their expression of the surface marker CD133. However, we also observed heterogeneity and instability of the TIC phenotype with disease progression. We examined whether instability in the TIC phenotype may be due to the acquisition of additional genetic alterations in the CD133- compared to the CD133+ fraction. Preliminary analysis suggests that most genetic alterations are common in both fractions; however, in 3/6 cases, additional genetic alterations were observed in the CD133- fraction, suggesting the emergence of CD133- TIC might be, at least in part, genetically driven. The mechanism of genetic instability is currently under investigation. In addition, we have used expression microarrays to examine differences between CD133+ and CD133- populations. We find that >1000 probes are differentially expressed in these two groups. We have identified several pathways with altered expression in TIC-enriched fractions. The biological role of these pathways in HG-SOC is under investigation. Our ability to identify and characterize TIC in this disease may facilitate development of new and more effective therapeutic strategies for ovarian cancer, thereby benefitting patients with this devastating disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3318. doi:1538-7445.AM2012-3318

Serous ovarian cancer (SOC) is the leading cause of morbidity/mortality from gynecologic malignancy. Current therapies increase survival significantly, yet the vast majority of SOC patients (70-90%) die of their disease. Patients almost always respond to initial courses of standard-of-care (platinum- and taxane-based) chemotherapy. Unfortunately, however, drug resistance almost always develops, resulting in the death of the patient. Two competing theories have been proposed to account for tumor initiation in SOC (and other malignancies); these theories also have important implications for therapy resistance. In the stochastic model, most, if not all, tumor cells can self-renew indefinitely; consequently, nearly all tumor cells provide a target population for the acquisition of drug resistance mutations. By contrast, the cancer stem cell (CSC) hypothesis holds that only a subset of tumor cells can initiate and maintain the tumor. Moreover, CSC might be intrinsically more resistant to some/many drugs that are effective against other (“bulk”) tumor cells. These two models differ fundamentally in their view of tumor-initiating cells (TIC). The essential feature of the CSC model is that tumors are organized hierarchically, such that TIC can be prospectively distinguished from non-TIC by phenotype. If the CSC model holds, it should be possible to identify and purify a stable cell population with the unique ability to generate serially transplantable tumors that recreate the heterogeneity of the initial malignancy. By contrast, the stochastic model predicts that TIC distribute into all cell fractions. Many studies of ovarian carcinogenesis and drug response have used immortalized cell lines grown for long periods of time in serum-containing culture. However, the extent to which these cells represent the biology of SOC is unclear. Many SOC lines do not reproduce serous histology when propagated as xenografts in immune-compromised mice; others cannot even give rise to xenografts. Even in culture, few of these lines show evidence of the cytologic and immunologic heterogeneity typically seen in primary tumors. Consequently, these lines might not be adequate for testing new therapies for SOC. Moreover, it is not clear that immortalized cell lines represent valid models for evaluating the CSC model or for studying TIC in SOC. Notably, studies of several other malignancies have shown that TIC as defined using immortalized cell lines do not have the same phenotype as those defined in xenografts using primary patient samples. Improving outcome for SOC patients will require better understanding of SOC pathogenesis and drug resistance, using assay systems that reflect the genetic and cellular diversity of human SOC more faithfully than conventional ovarian cancer cell lines. To this end, we have established a large collection of primary human SOC samples and developed a robust, quantitative assay for SOC tumor-initiating cells (TIC). Using this assay, we find that TICs are rare when assayed in either NOD/SCID or NOD/SCID/IL2Rγ−/− (NSG) mice. TIC frequency varies substantially between patients, although it is similar in primary ovarian masses and omental metastases, suggesting that TIC frequency is an intrinsic property of given ovarian tumor classes. For instance, CD133 marks all TICs from several primary SOC cases. However, in other cases, substantial TIC activity is found in both the CD133+ and CD133− fractions, whereas still other cases have exclusively CD133− TICs. Furthermore, the TIC phenotype can change in xenografts: primary tumors in which all TICs are CD133+ can give rise to xenografts that contain substantial numbers of CD133− TICs. Our results highlight the need for quantitative rigor in the evaluation of TICs and for caution when using passaged xenografts for such studies. Furthermore, although our data suggest that SOC conforms to the CSC hypothesis, the heterogeneity of the TIC phenotype may complicate its clinical application. To address whether instability in the TIC phenotype may be due to the acquisition of genetic alterations in the CD133- compared to the CD133+ fraction, we analyzed copy number alterations in CD133 positive and negative-derived xenografts. Preliminary analysis suggests that most genetic alterations are common in both fractions; however, in 3/6 cases, additional genetic alterations were observed in the CD133- fraction, suggesting the emergence of CD133- TIC might be, at least in part, genetically driven. The applicability of this observation to additional cases and primary sorted cells (i.e. those that were used to establish the xenografts), as well as the mechanism of genetic instability is currently under investigation. We used expression microarrays to examine differences between CD133+ and CD133- populations. We find that >1000 probes are differentially expressed in these two cell subsets, confirming that they are distinct cell populations. We have identified several putatively targetable pathways and transcription factor networks with altered expression in TIC-enriched fractions. The biological roles of these pathways in HG-SOC, specifically in the TIC compartment, are under investigation. Finally, we performed high-throughput flow cytometry: involving independent analysis of 365 cell surface markers to identify proteins expressed on all or subsets of HG-SOC cells. We have combined these analyses with mass cytometry (collaboration with Nolan's lab, Stanford University). Mass cytometry allows deep profiling of cell attributes and function using a novel multi-parametric approach combining flow cytometry with mass spectrometry that allows examination of up to 35 cell surface and/or intracellular markers on a single cell. Examination of 40 primary ovarian cancer samples has provided further supportive evidence for inter- and intra-patient heterogeneity in HG-SOC. Current analyses focus on biological validation of identified subpopulations marked by a series of cell surface and putative “stem cell” gene sets. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY35-02. doi:1538-7445.AM2012-SY35-02

Serous ovarian cancer (SOC) typically presents with advanced disease. Current therapy significantly increases survival, yet nearly all patients recur within five years and die of their disease. The cancer-initiating cell (CIC) hypothesis holds that only a subset of cells have the potential to extensively self-renew and give rise to other tumor cells. As their properties may differ from bulk tumor cells, CIC may be spared by available therapies. Identification and characterization of CIC may lead to more effective therapeutic strategies. Previous reports suggested the presence of ovarian CIC, but these findings require validation in primary human samples. Primary SOC were dissociated and depleted of CD45+ cells. Cell surface (CD133/CD44/CD117/CDCP1/MUC-1/VEGFR2) and functional (ALDH1) markers were examined by flow cytometry (n=105). All markers demonstrated intra-/inter-tumor heterogeneity; however only CD133, VEGFR2 and ALDH marked minority populations in all samples. In contrast to a report that CD44+/CD117+ cells identify ovarian CIC, CD117 was present on only half of SOC samples examined (N=75) and only one quarter had a CD44+/CD117+ population. Limiting dilution analysis of primary SOC injected in the mammary fat pad of NOD/SCID mice (95% take at 106 cells) revealed the CIC frequency in primary tumors (n=13) and metastases (n=6 +5 matched) to be ∼1/40000 (n=13). The CIC frequency was significantly higher (∼1/9000) in primary and recurrent ascites (n=16, p=0.002). Xenografts could be passaged at least 3 times, providing evidence of self-renewal. The CIC frequency remained constant in nearly all xenografts from primary tumors, but increased substantially with passage of recurrences, suggesting greater genetic instability. CD133+ cells from primary tumors (n=2), matched metastases (n=2), ascites (n=6) and passage 1 xenografts (n=6) were enriched for CIC (1/300-1/4000), and all (or the vast majority) of CIC activity resided within the CD133+ fraction. Xenografts from CD133+ cells gave rise to CD133+ and CD133- cells and could be serially passaged at least 1-3x. VEGFR2+ and ALDH1+ cells also were enriched for CIC, to a lower extent than CD133. In contrast, after sorting for CD117/CD44 (n=3), tumors arose from all fractions but CD117+/CD44+ cells. Our data are consistent with a hierarchical model of SOC and indicate that CD133 is a marker for ovarian CIC. Current work is devoted to profiling the CD133+ population and identifying additional markers, using high throughput flow cytometry and a panel of 234 antigens and other methods. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4303.