The occurrence of endometriosis with ovarian carcinomas is not purely coincidental

Objective

To explore the association between epithelial ovarian cancer (EOC) and common benign gynecological disorders.

Study design

The medical records of 226 patients with EOC treated at Peking Union Medical College Hospital between March 2011 and March 2012 were reviewed. Histological evaluations had been performed to determine the presence of coexisting pelvic endometriosis (n = 17), uterine leiomyoma (n = 66), adenomyosis (n = 22), or endometrial polyps (n = 17).

Results

Coexistence of endometriosis occurred in 35.3% and 36.4% of cases of the clear cell and endometrioid subtypes of EOC histology, respectively. Endometriosis was more likely associated with clear cell or endometrioid ovarian carcinoma, but less likely with high grade serous cancer. No differences were observed in the concurrence of uterine myoma, adenomyosis or endometrial polyps among the different subtypes of EOC.

Conclusions

In contrast to other common benign gynecological disorders, endometriosis showed close relationships with the clear cell and endometrioid subtypes of EOC specifically.     

Endosalpingiosis as it relates to tubal,ovarian and serous neoplastic tissues: An immunohistochemical study of tubal and Müllerian antigens

Objective

The origins and clinical significance of endosalpingiosis (ES), ectopic tubal epithelium, are not well understood. These investigations aim to characterize ES as it relates to normal fallopian tube, ovarian surface and serous neoplasms.

Methods

A retrospective review of pathology reports from all prophylactic gynecologic surgeries from 2000 to 2010 was performed to assess the frequency of ES. Twenty-one archival specimens of ES, 6 normal fallopian tubes, 9 normal ovaries, 21 serous neoplasms and a commercially available ovarian tissue microarray were subjected to immunohistochemistry (IHC) with 11 tubal and Müllerian antigens. IHC staining was evaluated with a quantitative scoring system and scores were analyzed using MINITAB statistical software.

Results

ES was noted in 3.5% of pathologic specimens from 464 prophylactic surgeries. The majority of antigens showed no significant differences (p > 0.05) in median IHC scores between ES and normal fallopian tube epithelium (nFTE), while they were significantly different (p < 0.05) from the ovarian surface epithelium (OSE). Median IHC scores were unchanged in ES tissues regardless of the location of ES or the presence of a concurrent serous neoplasm. Three antigens emerged as contemporary tubal and ES biomarkers: phospho-Smad2, BCL2 and FOXJ1. All 3 biomarkers were expressed in ES, nFTE and serous neoplasms, but not in OSE or other tumor types.

Conclusion

This study provides immunophenotypic evidence that ES is more similar to the nFTE than OSE. Further, ES biomarker expression closely resembles serous neoplasms strengthening the growing body of evidence that all Müllerian serous carcinomas arise from tubal-like epithelium.     

White blood cell differential counts in patients with polycystic ovary syndrome: a pilot study on Chinese women

Objective

A state of systemic chronic low grade inflammation has been observed in polycystic ovary syndrome (PCOS). It has been suggested that inflammation is a potential mechanism influencing the ovaries or endocrine system and might therefore contribute to the pathophysiology of PCOS. The aim of this study was to compare the total white blood cell (WBC), neutrophil granulocyte and lymphocyte differential counts between women with PCOS and controls. In addition, we estimated if the WBC differential counts had a relationship with body mass index (BMI), total testosterone levels, estradiol levels and luteinizing hormone levels of women with PCOS.

Study design

1016 subjects with PCOS and 1016 age-matched healthy women from a Han Chinese population were enrolled in this case–control study. Blood samples were taken from all the patients and controls to test total WBC counts, lymphocyte counts, neutrophil counts and related serum hormones.

Results

Total WBC counts and lymphocyte counts were elevated in PCOS subjects (t-test P < 0.01). Higher lymphocyte counts which contributed to higher total WBC counts in PCOS women were compared to age-matched controls. When the data were adjusted by BMI, the difference of WBC counts and lymphocyte counts between patients and controls remained significant.

Conclusions

The state of chronic low grade inflammation in patients with PCOS might be associated with immunological factors. Obesity and hyperandrogenism may be due to the underlying low grade inflammation.     

Overexpression of c-Abl predicts unfavorable outcome in epithelial ovarian cancer

Objectives

Abelson tyrosine kinase (c-Abl) has been shown to promote solid tumor invasion and metastasis. However, little is known regarding whether c-Abl contributes to the development or progression of epithelial ovarian cancer (EOC). The aims of this study are to determine the expression of c-Abl and investigate a possible relationship between c-Abl and prognosis in EOC.

Methods

c-Abl protein level was evaluated in 137 EOC specimens by immunohistochemical staining and 32 EOC specimens by Western blot analysis. Expression of c-Abl in ovarian cancer cell lines was measured by Western blot analysis and immunofluorescence. Survival analysis was performed to assess the correlation between c-Abl expression and survival.

Results

Immunohistochemical staining and Western blot analysis revealed that c-Abl was overexpressed in EOC compared with samples from a non-invasive ovarian tumor and normal ovaries (P < 0.05). Furthermore, expression of c-Abl was significantly associated with advanced FIGO stage, poor grade, serum Ca-125 and residual tumor size (P < 0.05). By Western blot analysis, c-Abl expression was examined in four ovarian cancer cell lines. Meanwhile, immunofluorescence was performed to show c-Abl expression in SKOV3 and 3AO cell lines. Survival analysis demonstrated that patients with low c-Abl staining had a significantly better survival compared to patients with high c-Abl staining (P < 0.05). In multivariate analysis, c-Abl overexpression, poor grade, advanced stage and suboptimal surgical debulking were independent prognostic factors of poor survival.

Conclusions

Our present study finds that c-Abl overexpression is associated with an unfavorable outcome. c-Abl may be a crucial predictor for EOC metastasis.     

High GMFG expression correlates with poor prognosis and promotes cell migration and invasion in epithelial ovarian cancer

Objective

The aim of this study was to characterize the clinical significance of GMFG, a novel ADF/cofilin superfamily protein, and investigate its role in cell migration and invasion in epithelial ovarian cancer (EOC).

Methods

The expression of GMFG in EOC tissues and ovarian cancer cell lines was evaluated by immunohistochemistry and immunoblotting respectively. The data were statistically analyzed for the associations of GMFG expression with clinicopathologic parameters and survival. In vitro cell migration and invasion assays were performed to determine the role of GMFG in cell migratory behaviors. The effect of GMFG on reorganization of actin cytoskeleton was investigated by immunostaining.

Results

GMFG was overexpressed in EOC. Up-regulated GMFG expression was closely correlated with advanced FIGO stage and chemoresistance of the disease. EOC patients with higher GMFG expression showed poorer progression-free survival (PFS) and overall survival (OS). In vitro cellular assays revealed that GMFG promoted cell migration and invasion. GMFG expression altered actin cytoskeleton organization probably by interacting with the Arp2/3 complex.

Conclusion

GMFG expression independently predicts poorer prognosis in patients with EOC. Ectopic overexpression of GMFG contributes to the malignant biological behavior of ovarian cancer cells.     

Prognostic and diagnostic significance of DNA methylation patterns in high grade serous ovarian cancer

Objective

Altered DNA methylation patterns hold promise as cancer biomarkers. In this study we selected a panel of genes which are commonly methylated in a variety of cancers to evaluate their potential application as biomarkers for prognosis and diagnosis in high grade serous ovarian carcinoma (HGSOC); the most common and lethal subtype of ovarian cancer.

Methods

The methylation patterns of 10 genes (BRCA1, EN1, DLEC1, HOXA9, RASSF1A, GATA4, GATA5, HSULF1, CDH1, SFN) were examined and compared in a cohort of 80 primary HGSOC and 12 benign ovarian surface epithelium (OSE) samples using methylation-specific headloop suppression PCR.

Results

The genes were variably methylated in primary HGSOC, with HOXA9 methylation observed in 95% of cases. Most genes were rarely methylated in benign OSE, with the exception of SFN which was methylated in all HGSOC and benign OSE samples examined. Methylation of DLEC1 was associated with disease recurrence, independent of tumor stage and suboptimal surgical debulking (HR 3.5 (95% CI:1.10-11.07), p = 0.033). A combination of the methylation status of HOXA9 and EN1 could discriminate HGSOC from benign OSE with a sensitivity of 98.8% and a specificity of 91.7%, which increased to 100% sensitivity with no loss of specificity when pre-operative CA125 levels were also incorporated.

Conclusions

This study provides further evidence to support the feasibility of detecting altered DNA methylation patterns as a potential diagnostic and prognostic approach for HGSOC.     

Assessment of preoperative serum prolidase activity in epithelial ovarian cancer

Objective

Prolidase is a cytosolic exopeptidase that cleaves iminodipeptides with C-terminal proline and hydroxyproline and plays a major role in collagen turnover. The aim of this study was to evaluate preoperative serum prolidase activity, total oxidant status (TOS), and total antioxidant capacity (TAC) in patients with newly diagnosed epithelial ovarian cancer (EOC).

Study design

Serum prolidase activity, TOS, and TAC were measured spectrophotometrically in both EOC cases (n = 28) and controls (n = 28).

Results

Preoperative serum prolidase activity and TOS were significantly higher in patients with EOC compared to controls (p = 0.009 and 0.008, respectively), whereas TAC was significantly lower in cases (p < 0.001). A significant positive correlation was found between the stage, grade, and CA-125 level of EOC and serum prolidase activity (rho = 0.466, p = 0.012; rho = 0.501, p = 0.007; and rho = 0.447, p = 0.017, respectively) and TOS (rho = 0.588, p = 0.001; rho = 0.412, p = 0.029; and rho = 0.568, p = 0.002, respectively). In contrast, there was a negative correlation between TAC and the stage, grade, and CA-125 level of EOC (rho = −0.555, p = 0.002; rho = −0.566, p = 0.002; and rho = −0.581, p = 0.001, respectively).

Conclusion

Findings of the present study demonstrate that serum prolidase activity is significantly associated with the stage, tumor grade, and preoperative CA-125 level of EOC.     

Placental glucose transporter 3 (GLUT3) is up-regulated in human pregnancies complicated by late-onset intrauterine growth restriction

Introduction

Transport of glucose from maternal blood across the placental trophoblastic tissue barrier is critical to sustain fetal growth. The mechanism by which GLUTs are regulated in trophoblasts in response to ischemic hypoxia encountered with intrauterine growth restriction (IUGR) has not been suitably investigated.

Objective

To investigate placental expression of GLUT1, GLUT3 and GLUT4 and possible mechanisms of GLUT regulation in idiopathic IUGR.

Methods

We analyzed clinical, biochemical and histological data from placentas collected from women affected by idiopathic full-term IUGR (n = 10) and gestational age-matched healthy controls (n = 10).

Results

We found increased GLUT3 protein expression in the trophoblast (cytotrophoblast greater than syncytiotrophoblast) on the maternal aspect of the placenta in IUGR compared to normal placenta, but no differences in GLUT1 or GLUT4 were found. No differential methylation of the GLUT3 promoter between normal and IUGR placentas was observed. Increased GLUT3 expression was associated with an increased nuclear concentration of HIF-1α, suggesting hypoxia may play a role in the up-regulation of GLUT3.

Discussion

Further studies are needed to elucidate whether increased GLUT3 expression in IUGR is a marker for defective villous maturation or an adaptive response of the trophoblast in response to chronic hypoxia.

Conclusions

Patients with IUGR have increased trophoblast expression of GLUT3, as found under the low-oxygen conditions of the first trimester.     

Diabetes mellitus and ovarian cancer: More complex than just increasing risk

Objective

Diabetes mellitus (DM) is a risk factor for endometrial cancer and is associated with poorer outcomes in breast and colon cancers. This association is less clear in epithelial ovarian cancer (EOC). We sought to examine the effect of DM on progression-free (PFS) and overall survival (OS) in women with EOC.

Methods

A retrospective cohort study of EOC patients diagnosed between 2004 and 2009 at a single institution was performed. Demographic, pathologic and DM diagnosis data were abstracted. Pearson chi-square test and t test were used to compare variables. The Kaplan–Meier method and the log rank test were used to compare PFS and OS between non-diabetic (ND) and DM patients.

Results

62 (17%) of 367 patients had a diagnosis of DM. No differences in age, histology, debulking status, or administration of intraperitoneal chemotherapy between ND and DM patients were present, although there were more stage I and IV patients in the ND group (p = 0.04). BMI was significantly different between the two groups (ND vs. DM, 27.5 vs. 30.7 kg/m², p < 0.001). While there were no differences in survival based on BMI, diabetic patients had a poorer PFS (10.3 vs. 16.3 months, p = 0.024) and OS (26.1 vs. 42.2 months, p = 0.005) compared to ND patients. Metformin use among diabetic patients did not appear to affect PFS or OS.

Conclusions

EOC patients with DM have poorer survival than patients without diabetes; this association is independent of obesity. Metformin use did not affect outcomes. The pathophysiology of this observation requires more inquiry.     

Variation of DNA methylation in candidate age-related targets on the mitochondrial-telomere axis in cord blood and placenta

Background

Epigenetics is tissue-specific and potentially even cell-specific, but little information is available from human reproductive studies about the concordance of DNA methylation patterns in cord blood and placenta, as well as within-placenta variations. We evaluated methylation levels at promoter regions of candidate genes in biological ageing pathways (SIRT1, TP53, PPARG, PPARGC1A, and TFAM), a subtelomeric region (D4Z4) and the mitochondrial genome (MT-RNR1, D-loop).

Methods

Ninety individuals were randomly chosen from the ENVIRONAGE birth cohort to evaluate methylation concordance between cord blood and placenta using highly quantitative bisulfite-PCR pyrosequencing. In a subset of nineteen individuals, a more extensive sampling scheme was performed to examine within-placenta variation.

Results

The DNA methylation levels of the subtelomeric region and mitochondrial genome showed concordance between cord blood and placenta with correlation coefficients ranging from r = 0.31 to 0.43, p ≤ 0.005, and also between the maternal and foetal sides of placental tissue (r = 0.53 to 0.72, p ≤ 0.05). For the majority of targets, an agreement in methylation levels between four foetal biopsies was found (with intra-class correlation coefficients ranging from 0.16 to 0.72), indicating small within-placenta variation.

Conclusions

The methylation levels of the subtelomeric region (D4Z4) and mitochondrial genome (MT-RNR1, D-loop) showed concordance between cord blood and placenta, suggesting a common epigenetic signature of these targets between tissues. Concordance was lacking between the other genes that were studied. In placental tissue, methylation patterns of most targets on the mitochondrial-telomere axis were not strongly influenced by sample location.     

Defective expression of Protein 4.1N is correlated to tumor progression,aggressive behaviors and chemotherapy resistance in epithelial ovarian cancer

Objective

Protein 4.1N (4.1N) is a member of the Protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. In this study, we evaluated the expression of 4.1N protein and its potential roles in epithelial ovarian cancer (EOC) tumorigenesis and progression.

Methods

4.1N protein expression was investigated in a total of 280 samples including 74 normal tissues, 35 benign, 30 borderline and 141 malignant epithelial ovarian tumors by immunohistochemistry. Correlation between 4.1N expression levels and clinicopathologic features was statistically analyzed. The expression of 4.1N in EOC cell lines was examined by western blotting.

Results

Immunohistochemistry analysis revealed that, although there was no loss of 4.1N expression in normal tissues and benign tumors, absence of Protein 4.1N was significantly more common in EOCs (44.0%) than in borderline tumors (3.3%) (p < 0.001). Furthermore, loss or decreased expression of 4.1N protein expression was correlated with malignant potential of the tumors (14.3% in benign tumors, 56.7% in borderline tumors and 92.9% in malignancy) (p < 0.001). In EOC samples, loss of 4.1N protein was significantly associated with advanced-stage (p = 0.004), ascites (p = 0.009), omental metastasis (p = 0.018), suboptimal debulking (p = 0.024), poorly histological differentiation (p = 0.009), high-grade serous carcinoma (p = 0.001), short progression-free-survival (p = 0.018) and poor chemosensitivity to first-line chemotherapy (p = 0.029). Moreover, western blotting analysis revealed that expression of 4.1N protein was lost in 4/8 (50%) EOC cell lines.

Conclusions

4.1N protein expression level was significantly decreased during malignant transformation of epithelial ovarian tumors and that loss of 4.1N expression was closely correlated to poorly differentiated and biologically aggressive EOCs.     

Polymorphic variants of DNMT3A and the risk of endometriosis

Objective

Overexpression of DNA methyltransferase 3A (DNMT3A) and aberrant methylation of various genes in eutopic endometrium have been demonstrated in women with endometriosis. We aimed to study whether DNMT3A polymorphisms could be a genetic risk factor for endometriosis and endometriosis-related infertility.

Study design

We studied 5 SNPs (rs2289195, rs7590760, rs13401241, rs749131 and rs1550117) located in the DNMT3A gene in 357 women with endometriosis and 640 controls.

Results

We did not observe significant differences between genotype and allele frequencies of rs2289195, rs7590760, rs13401241, rs749131 and rs1550117 SNPs in women with endometriosis, endometriosis-related infertility, and controls. The lowest p values of the trend test were observed for DNMT3A rs1550117 in endometriosis and endometriosis-related infertility (p_trend = 0.049 and p_trend = 0.055, respectively).

Conclusions

Our results did not supply evidence for the contribution of SNPs located in DNMT3A to either endometriosis or endometriosis-related infertility.     

Overlapping DNA methylation profile between placentas with trisomy 16 and early-onset preeclampsia

Introduction

Maternal preeclampsia is associated with altered placental development in the first trimester of pregnancy. Confined placental trisomy 16 mosaicism (CPM16) is a genetic abnormality of the placenta that is highly predisposing to preeclampsia. We previously demonstrated widespread alterations in DNA methylation in 3rd trimester placentae associated with chromosomally normal early-onset preeclampsia (EOPET) and questioned whether similar changes would be associated with CPM16, making this condition a potential model for studying EOPET-associated changes early in pregnancy.

Methods

Using the Illumina Infinium HumanMethylation450 BeadChip, 3rd trimester CPM16 placental samples (N = 10) were compared to gestational age matched controls, and to 1st trimester trisomy 16 placentae (N = 5).

Results

DNA methylation differences associated with CPM16 were identified at 2254 CpGs using stringent criteria (FDR < 0.01, Δβ > 0.15). A subset of these differences (11%; p < 0.0001) overlapped those observed in chromosomally normal EOPET using similarly stringent criteria (FDR < 0.01; Δβ > 0.125). Importantly, the majority of EOPET-associated CpGs were significantly altered (p < 0.05) in CPM16 with a similar Δβ distribution. This was true for CPM16 with (N = 5) and without (N = 5) EOPET, although EOPET cases showed a tendency towards larger changes. Of the shared CPM16/EOPET associated changes, three CpGs near two genes (ARGHEF37 and JUNB) were also altered in 1st trimester trisomy 16 placentae.

Discussion

Despite the limited sample size, widespread DNA methylation changes are observed in Trisomy 16 that overlap those seen previously in chromosomally normal EOPET. Hence, Trisomy 16 may provide a model to study the progression of placental changes that occurs in EOPET across different gestational ages.     

Small-for-gestational-age fetuses with normal umbilical artery Doppler have suboptimal perinatal and neurodevelopmental outcome

Objective

To evaluate the perinatal and neurodevelopmental outcome of small-for-gestational-age fetuses with normal umbilical artery Doppler managed expectantly during pregnancy and delivery.

Study design

Perinatal and neurodevelopmental outcome was assessed from a cohort of singleton small-for-gestational-age fetuses with normal umbilical artery Doppler and normally grown controls matched by gestational age at delivery, parity and parental socio-economic level. Neurodevelopmental outcome was prospectively evaluated by means of the 24-month Age&Stage Questionnaire (ASQ).

Results

A total of 129 small-for-gestational-age fetuses and 259 controls were included. Small-for-gestational-age fetuses had a higher risk for neonatal intensive care unit admission (15.5% versus 3.9%; p < 0.001) and significant neonatal morbidity (2.3% versus 0%; p = 0.04) than controls. At 24-months, these fetuses showed significantly lower neurodevelopmental centile in the problem solving (42.8 versus 52.1; p = 0.001) and personal-social (44.4 versus 54.6; p < 0.001) areas than controls.

Conclusion

Perinatal and neurodevelopmental outcome in small-for-gestational-age fetuses with normal umbilical artery Doppler is suboptimal, which may challenge the role of umbilical artery Doppler to discriminate between normal-SGA and growth-restricted fetuses.     

Spatial and temporal changes of Decorin,Type I collagen and Fibronectin expression in normal and clone bovine placenta

Introduction

Alteration of expression of various genes including extracellular matrix components, have been suggested to play major role in the placental pathologies after somatic cloning in mammals. The objectives of the present study were to analyze pattern of expression (mRNA and protein) of the small leucine-rich proteoglycan, Decorin in association with Type I Collagen and Fibronectin in bovine placental tissues from normal and clone pregnancies.

Methods

Genotyping and allelic expression of Decorin were determined by Sanger sequencing. The expression patterns of Decorin, Type I collagen and Fibronectin 1 were analyzed by quantitative RT-qPCR and combined in situ hybydization (ISH) and immunohistochemistry (IHC) in endometrial and placental tissues from D18 to term from artificially inseminated and somatic cloning pregnancies.

Results

The expression levels of DCN increased in the AI endometrial stroma and chorionic mesenchyme during implantation and declined during placentome growth until term. Combined ISH and IHC revealed an unexpected discrepancy mRNA and protein tissue distribution. Moreover, Decorin was maintained in the placentome tissues from SCNT pregnancies while both mRNA and protein were absent in AI derived placenta.

Discussion

In bovine, the pattern of expression of Decorin exhibits significant changes during placental formation. Downregulation of Decorin is associated with proliferation, remodeling and vascularization of placental tissues. These observations reinforces the putative role of Decorin in these processes.

Conclusions

These observations suggest that Decorin is involved in placental growth and that dysregulation of its expression is associated with placental abnormalities in SCNT derived pregnancy.     

Novel expression of CD11b in epithelial ovarian cancer: Potential therapeutic target

Objective

The objective of this study was to determine the expression, and effect of targeting CD11b with a monoclonal antibody in ovarian cancer cells.

A prospective comparison of integrated FDG-PET/contrast-enhanced CT and contrast-enhanced CT for pretreatment imaging of advanced epithelial ovarian cancer

Objective

The use of tumor debulking surgery in the management of epithelial ovarian cancer (EOC), which is often disseminated in the peritoneal cavity at the time of diagnosis, has a significant impact on prognosis. We compared ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/contrast-enhanced computed tomography (PET/CT) to contrast-enhanced CT for the detection of dissemination into the abdominal cavity preventing successful primary debulking surgery.

Methods

Forty-one women with EOC underwent preoperative whole-body low-dose FDG-PET/CT followed by diagnostic high dose contrast-enhanced CT scan, and the results were compared with systematically recorded surgical findings as a reference standard. Both site-based and patient-based analyses were conducted.

Results

FDG-PET/CT was superior to conventional CT for the detection of carcinomatosis in subdiaphragmatic peritoneal surfaces (p = 0.020) and in the bowel mesentery (p = 0.001). Patient-based analysis of upper abdominal areas requiring extensive surgical procedures showed no significant differences between the two imaging methods. The sensitivity of PET/CT and CT was poor in certain areas of the peritoneal cavity (64% vs. 27% in the small bowel mesentery and 65% vs. 55% in the right upper abdomen). Extra-abdominal disease spread was detected by PET/CT in 32 patients and by CT in 25 patients.

Conclusions

PET/CT was not superior to CT for the detection of intra-abdominal disease spread. Patients with suspected EOC should be referred for upfront radical surgery regardless of the results of preoperative imaging studies. PET/CT is more effective for the detection of extra-abdominal disease than CT, but the clinical significance of this finding is unclear.     

Prognostic analysis of invasive circulating tumor cells (iCTCs) in epithelial ovarian cancer

Goals

Circulating tumor cells (CTCs) have been introduced as a biomarker in detecting advanced epithelial ovarian cancer (EOC). The goals are to examine the prevalence of the invasive subpopulation of CTCs (iCTCs) in patients at high risk of EOC and to compare this biomarker to serum CA125.

Methods

We used a unique cell adhesion matrix (CAM)-based, functional cell enrichment and identification platform to isolate iCTCs from 129 preoperative patients. We confirmed the identity of iCTCs using positive epithelial (Epi +) markers and negative hematopoietic lineage (HL −) markers. Sensitivity and specificity of the assays were examined and iCTCs/CA125 were correlated with overall survival (OS), progression-free survival (PFS) and clinical parameters.

Results

We found a 41.2% sensitivity, 95.1% specificity and 77.8% positive predictive value (PPV) of the iCTC assay in detecting patients with stage I and II EOC malignancy, and a 83% sensitivity and 97.3% PPV in detecting all stages of EOC malignancy. However, a positive CA125 test provided weak evidence to detect stage I and II malignancy (61.6% PPV) and all EOC (92.1% PPV), because of its 76.2% specificity. A significantly stronger concordance in OS and PFS of clinical factors (tumor stage, debulking and platinum sensitivity) was noted for elevated iCTCs than for serum CA125.

Conclusion

The CAM-initiated CTC enrichment/identification method enabled the detection of early stage EOC. iCTCs were better correlated with worse OS and PFS, more specific and better PPV than CA125 in detecting EOC malignancy in patients at high risk of EOC.