Factor In Epithelial Ovarian Cancer Research Articles

Risk factors of epithelial ovarian carcinomas among women with endometriosis: a systematic review.

The objective of this review was to evaluate the published literature on epidemiologic risk factors for epithelial ovarian cancer among women with a diagnosis of endometriosis. A systematic literature search was conducted in PubMed and Scopus. Studies comparing epidemiologic risk factors of epithelial ovarian cancer among women with endometriosis were included. A quality assessment was conducted using the Newcastle-Ottawa Scale. Eight of 794 articles met the inclusion criteria. A lower risk of epithelial ovarian cancer was observed in women with documented complete surgical excision of endometriotic tissue and suggested among women with unilateral oophorectomy. The use of oral contraceptives (≥10 years) may be associated with a lower risk of epithelial ovarian cancer among women with endometriosis, whereas older age at endometriosis diagnosis (≥45 years, pre- or postmenopausal), nulliparity, hyperestrogenism (endogenous or exogenous), premenopausal status at endometriosis diagnosis, solid compartments as well as larger size of endometrioma (≥9 cm in diameter at endometriosis diagnosis) were all associated with an increased risk of ovarian cancer. A subgroup of women with endometriosis characterized by endometriosis observed through surgery or imaging after the age of 45 years, nulliparity, postmenopausal status at endometriosis diagnosis, larger size of endometrioma (>9 cm) at endometriosis diagnosis, hyperestrogenism (endogenous or exogenous) and/or cysts with solid compartments may have an elevated risk of epithelial ovarian cancer. However, due to the limited number and size of studies in this area we cannot draw definitive conclusions. Further research into a risk factor profile among women with endometriosis is needed before clear recommendations can be made.

Chronic Recreational Physical Inactivity and Epithelial Ovarian Cancer Risk

It is estimated that 5% of women in the United States and 10% to 50% of women worldwide are physically inactive. Previous studies have demonstrated that recreational physical activity is associated with decreased risks of developing breast, colon, and endometrial cancers. The association between physical activity and epithelial ovarian cancer (EOC) is less clear. Despite extensive research, including several epidemiological studies and 2 systematic reviews, insufficient and inconsistent evidence is available to support an independent association between recreational physical activity and risk of EOC. This is largely due to use of common methodology in most studies that overlooks recreational physical inactivity as an independent risk factor for EOC.

262 - The expression of cyclooxygenase-2 is increased by nerve growth factor in epithelial ovarian cancer

262 - The expression of cyclooxygenase-2 is increased by nerve growth factor in epithelial ovarian cancer

Neoadjuvant chemotherapy is superior to primary debulking surgery in patients with presumed unresectable epithelial ovarian cancer

Objectives: We sought to: (1) identify prognostic factors in epithelial ovarian cancer (EOC) treated with neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS), and (2) compare overall (OS) and progression-free survival (PFS) between NACT for presumed unresectable disease versus suboptimal primary debulking surgery (PDS). Methods: This was a retrospective study of consecutive patients undergoing IDS after NACT at our institution from 2007 to 2013. Clinical factors were abstracted from medical records and complete clinical response (CCR) was defined as no gross disease at IDS. Survival times were estimated with the Kaplan-Meier method and compared using the log-rank test. The subset of patients receiving NACT for the indication of presumed unresectable disease were matched 1:1 on age and stage with a contemporary cohort of patients receiving suboptimal PDS between 2003 and 2011. Survival times were compared using stratified Cox models to account for the varying duration of follow-up within each matched pair. Results: Eighty-eight patients were treated with NACT/IDS, and median PFS and OS were 1.3 and 2.6 years, respectively. The following factors were associated with improved survival after NACT: normalization of CA-125 before IDS (median OS 3.0 vs 1.9 years, P = .02); age less than 65 (3.3 vs 1.9 years, P = .005); CCR at IDS (5.6 vs 2.5 years, P = .15), and no gross residual disease after IDS (2.9 vs 2.2 years, P = .06). We saw no association between survival and number of post-IDS chemotherapy cycles, 3 vs more than 3 cycles, including among those with persistently elevated CA-125 at IDS (median OS 2.2 vs 2.7 years, P = 0.63). In our matched comparison of unresectable cases treated with NACT versus suboptimal PDS, we observed a significant OS advantage for NACT (HR 0.46, 95% CI 0.23–0.92), with no significant difference in PFS. Conclusions: We saw no survival benefit with increasing duration of adjuvant chemotherapy after IDS, but selection bias likely minimizes the benefit in partial responders. Young age, clinical response, and residual disease are all likely predictors of OS. For primary EOC in which resection to residual disease less than 1 cm is unlikely, NACT is associated with longer survival than PDS. Analysis of morbidity and costs are ongoing. As these patients are likely best served by NACT, more reliable predictors of resectability are needed to better identify such cases.

Analysis of immune-related prognostic markers in colon cancer patients randomized to surgery or surgery and adjuvant cytostatic treatment.

e15102Background: HLA-A*02, a common allele in the Scandinavian population, is a negative prognostic factor in epithelial ovarian cancer. It is a strong predictor of patient outcome, only inferior ...

Head-to-head comparison of the impact of Aurora A, Aurora B, Repp86, CDK1, CDK2 and Ki67 expression in two of the most relevant gynaecological tumor entities.

The dysregulation of cell cycle kinases plays a crucial role in carcinogenesis and the expression of various kinases has been attributed to aggressive tumor growth and an unfavourable prognosis in oncological patients. We, therefore, aimed to evaluate the expression of Ki67 among five additional cell cycle kinases in a collective of mammary and ovarian tumor specimens and to find a correlation with clinicopathological parameters. 76 mammary and 93 ovarian benign and malignant tumor samples were immunohistochemically stained and evaluated for the expression of Aurora A and B, Repp86, CDK1 and 2 (only breast specimens) and Ki67. The expression patterns of these cell cycle kinases were matched with retrospectively collected clinicopathological parameters. All examined cell cycle kinases accurately discriminated benign from malignant breast and ovarian tissues. In breast cancer, Aurora A and B-, Repp86-, CDK2- and Ki67-expression was inversely associated with ER expression. No correlation with the HER2-status was found in our collective. Importantly, we found a significant correlation between the expression of Aurora A and CDK1 and axillary lymph node metastasis in breast cancer. Furthermore, a shortened disease free survival (DFS) upon expression of Aurora B and CDK2 was shown in breast cancer patients. None of the cell cycle kinases was associated with predictive or prognostic factors in epithelial ovarian cancer. The prognostic value of the expression of Ki67 is overtrumped by alternative cell cycle kinases when it comes to prediction of axillary tumor spread and a shortened DFS, which might allow a further risk stratification in breast cancer patients.

Ubiquitin-specific protease 7 expression is a prognostic factor in epithelial ovarian cancer and correlates with lymph node metastasis.

ObjectiveUbiquitin-specific protease 7 (USP7) is a common target of herpesviruses and is important in the DNA damage response, which is also upregulated in several cancers, including prostate, colon, liver, and lung cancers. However, less is known about its expression in ovarian cancer tissues. The role of USP7 in epithelial ovarian cancer (EOC) has not yet been investigated.Materials and methodsWe recruited 141 patients from Linyi People’s Hospital between June 1999 and June 2013, all pathologically diagnosed with primary EOC. Their clinical data were collected, and the expression of USP7 in the tumor tissues was determined using immunohistochemistry. The correlations between USP7 expression and the clinicopathological variables of patients with EOC were assessed using Spearman’s rank correlation test. Kaplan–Meier analysis and Cox regression analysis were used to identify the prognosis value of USP7. The function of USP7 in the EOC cells was also detected in vitro.ResultsAmong the 141 cases, USP7 expression was high in 59 EOC samples (41.8%), and was significantly correlated with lymphatic invasion; USP7 can act as independent prognostic indicator for the overall survival (OS) of EOC, and its high expression was associated with poor OS rate. The RNA inteference and overexpression assays indicated that USP7 can positively regulate the ovarian cell vitality and invasion process.ConclusionPatients with EOC expressing high level of USP7 have worse OS compared with those with low USP7 expression. USP7 may be involved in the proliferation and invasion of EOC cells, and USP7 expression can serve as an independent predictor of EOC.

Cytokines and Prognostic Factors in Epithelial Ovarian Cancer.

INTRODUCTIONOvarian cancer has a high mortality and delayed diagnosis. Inflammation is a risk factor for ovarian cancer, and the inflammatory response is involved in almost all stages of tumor development. Immunohistochemical staining in stroma and epithelium of a panel of cytokines in benign and malignant ovarian neoplasm was evaluated. In addition, immunostaining was related to prognostic factors in malignant tumors.METHODThe study group comprised 28 ovarian benign neoplasias and 28 ovarian malignant neoplasms. A panel of cytokines was evaluated by immunohistochemistry (Th1: IL-2 and IL-8; Th2: IL-5, IL-6, and IL-10; and TNFR1). Chi-square test with Yates’ correction was used, which was considered significant if less than 0.05.RESULTSTNFR1, IL-5, and IL-10 had more frequent immunostaining 2/3 in benign neoplasms compared with malignant tumors. Malignant tumors had more frequent immunostaining 2/3 for IL-2 in relation to benign tumors. The immunostaining 0/1 of IL 8 was more frequent in the stroma of benign neoplasms compared with malignant neoplasms. Evaluation of the ovarian cancer stroma showed that histological grade 3 was significantly correlated with staining 2/3 for IL-2 (P = 0.004). Women whose disease-free survival was less than 2.5 years had TNFR1 stromal staining 2/3 (P = 0.03) more frequently.CONCLUSIONIL-2 and TNFR1 stromal immunostaining are related prognostic factors in ovarian cancer and can be the target of new therapeutic strategies.

Nutrient-wide association study of 57 foods/nutrients and epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study

Studies of the role of dietary factors in epithelial ovarian cancer (EOC) development have been limited, and no specific dietary factors have been consistently associated with EOC risk. We used a nutrient-wide association study approach to systematically test the association between dietary factors and invasive EOC risk while accounting for multiple hypothesis testing by using the false discovery rate and evaluated the findings in an independent cohort. We assessed dietary intake amounts of 28 foods/food groups and 29 nutrients estimated by using dietary questionnaires in the EPIC (European Prospective Investigation into Cancer and Nutrition) study (n = 1095 cases). We selected 4 foods/nutrients that were statistically significantly associated with EOC risk when comparing the extreme quartiles of intake in the EPIC study (false discovery rate = 0.43) and evaluated these factors in the NLCS (Netherlands Cohort Study; n = 383 cases). Cox regression models were used to estimate HRs and 95% CIs. None of the 4 dietary factors that were associated with EOC risk in the EPIC study (cholesterol, polyunsaturated and saturated fat, and bananas) were statistically significantly associated with EOC risk in the NLCS; however, in meta-analysis of the EPIC study and the NLCS, we observed a higher risk of EOC with a high than with a low intake of saturated fat (quartile 4 compared with quartile 1; overall HR: 1.21; 95% CI: 1.04, 1.41). In the meta-analysis of both studies, there was a higher risk of EOC with a high than with a low intake of saturated fat.

WWOX CNV-67048 Functions as a Risk Factor for Epithelial Ovarian Cancer in Chinese Women by Negatively Interacting with Oral Contraceptive Use.

Copy number variations (CNVs) have attracted increasing evidences to represent their roles as cancer susceptibility regulators. However, little is known about the role of CNV in epithelia ovarian cancer (EOC). Recently, the CNV-67048 of WW domain-containing oxidoreductase (WWOX) was reported to alter cancer risks. Considering that WWOX also plays a role in EOC, we hypothesized that the CNV-67048 was associated with EOC risk. In a case-control study of 549 EOC patients and 571 age (±5 years) matched cancer-free controls, we found that the low copy number of CNV-67048 (1-copy and 0-copy) conferred a significantly increased risk of EOC (OR = 1.346, 95% CI = 1.037–1.747) and it determined the risk by means of copy number-dependent dosage effect (P = 0.009). Data from TCGA also confirmed the abovementioned association as the frequency of low copies in EOC group was 3.68 times more than that in healthy group (P = 0.023). The CNV also negatively interacted with oral contraceptive use on EOC risk (P = 0.042). Functional analyses further showed a lower mRNA level of WWOX in tissues with the 0-copy or 1-copy than that in those with the 2-copy (P = 0.045). Our data suggested the CNV-67048 to be a risk factor of EOC in Chinese women.

Loss of ITM2A, a novel tumor suppressor of ovarian cancer through G2/M cell cycle arrest, is a poor prognostic factor of epithelial ovarian cancer

ObjectiveIntegral membrane protein 2A (ITM2A) is a type 2 transmembrane protein of unknown function. The aim of this study was to investigate its expression pattern, clinical significance, and biological function in epithelial ovarian cancer. MethodsITM2A expression in 35 normal, 20 adenoma, 11 borderline and 90 cancerous ovarian tissues was measured by immunohistochemistry. Clinicopathological parameters were obtained from medical records. Survival data was analyzed using Kaplan–Meier estimates and multivariate analysis using the Cox-regression method. Anti-tumor activities of ITM2A were explored by cell proliferation and colony formation assays, flow cytometry, Western blots and animal studies using ovarian cancer cell lines. Chemoresponsiveness was evaluated by measuring IC50 and confirmed by animal studies using an intraperitoneal orthotropic model. ResultsITM2A was significantly downregulated in invasive carcinomas compared to normal, adenoma and borderline tumor tissues. ITM2A loss occurred in 45.6% (41 of 90) of invasive carcinomas and was significantly associated with FIGO stage, type II tumors, suboptimal debulking operation, recurrence and chemoresistance. ITM2A loss and higher FIGO stage were independent factors for poor prognosis. Expression of ITM2A inhibited growth and induced G2/M cell cycle arrest by attenuating cdc2, cyclin B1, cdc25c and p-cdc2 (Thr 161). In vitro and in vivo experiments showed that ITM2A expression significantly reduced the paclitaxel and carboplatin IC50 and tumor mass after paclitaxel treatment. ConclusionITM2A is a new biomarker of poor prognosis in ovarian cancer. It is a novel tumor suppressor that induces cell cycle arrest, acts as a chemosensitizer, and has therapeutic potential for ovarian cancer.

Skeletal Muscle Depletion and Markers for Cancer Cachexia Are Strong Prognostic Factors in Epithelial Ovarian Cancer.

ObjectiveTumor cachexia is an important prognostic parameter in epithelial ovarian cancer (EOC). Tumor cachexia is characterized by metabolic and inflammatory disturbances. These conditions might be reflected by body composition measurements (BCMs) ascertained by pre-operative computed tomography (CT). Thus, we aimed to identify the prognostically most relevant BCMs assessed by pre-operative CT in EOC patients.MethodsWe evaluated muscle BCMs and well established markers of nutritional and inflammatory status, as well as clinical-pathological parameters in 140 consecutive patients with EOC. Furthermore, a multiplexed inflammatory marker panel of 25 cytokines was used to determine the relationship of BCMs with inflammatory markers and patient’s outcome. All relevant parameters were evaluated in uni- and multivariate survival analysis.ResultsMuscle attenuation (MA)—a well established BCM parameter—is an independent prognostic factor for survival in multivariate analysis (HR 2.25; p = 0.028). Low MA—reflecting a state of cachexia—is also associated with residual tumor after cytoreductive surgery (p = 0.046) and with an unfavorable performance status (p = 0.015). Moreover, MA is associated with Eotaxin and IL-10 out of the 25 cytokine multiplex marker panel in multivariate linear regression analysis (p = 0.021 and p = 0.047, respectively).ConclusionMA—ascertained by routine pre-operative CT—is an independent prognostic parameter in EOC patients. Low MA is associated with the inflammatory, as well as the nutritional component of cachexia. Therefore, the clinical value of pre-operative CT could be enhanced by the assessment of MA.

Abstract POSTER-BIOL-1301: The receptor tyrosine kinase AXL modulates oncogenic signaling and epithelial mesenchymal transition in epithelial ovarian cancer

Abstract Metastasis in epithelial ovarian cancer (EOC) is lethal, and results into a 5-year-survival rate lower than 30%. In EOC, tumor cells undergo Epithelial-Mesenchymal Transition (EMT) to attain the invasive and migratory potential crucial for metastasis. The analysis of molecular heterogeneity in EOC also demonstrated the important role of EMT. Our group has previously classified EOC tumors and cell lines into 5 distinct molecular subtypes based on their global gene expression patterns. Among these subtypes, the Mesenchymal subtype is believed to be driven by EMT. Receptor Tyrosine Kinases (RTKs), which play a pivotal role in proliferation and survival pathways, have been strongly indicated to mediate signals in EMT. Upon interrogating the kinome expression patterns by determining the top 10 ranked kinases in each molecular subtype, the RTK AXL was revealed to have a significantly high ranking in the Mesenchymal subtype. The purpose of this study is to elucidate the role of AXL in oncogenic signaling and EMT in EOC. Western Blotting of total Axl protein in a panel of 40 EOC cell lines revealed a distinctive pattern among the 5 molecular subtypes. Upon ligand activation by Gas6 in Axl-expressing cell lines, pERK and pAkt, two signaling molecules downstream of Axl, displayed a unique temporal signaling pattern specific to the Mesenchymal subtype. This resulted into an implication of the preferential sensitivity to Axl-specific inhibitors in the Mesenchymal subtype. The IC-50 of R428, one small molecule inhibitor specific to Axl, was significantly lower in the Mesenchymal cell lines compared to the other subtypes (Average of 2.91 μM versus 9.38 μM; p-value=0.01) Stable clones were generated by using shRNAs to knockdown AXL in Mesenchymal EOC lines. shAXL SKOV3 cells demonstrated a reversal of EMT evident by restoration of Ecadherin. siRNA mediated transient silencing of AXL showed a reduction in cell motility with decreased total displacement and velocity measured over 12 hours (31.98 μm compared to 44.59 μm, p-value=0.01; and 17.35 μm/second compared to 23.15 μm/second, pvalue= 0.03) measured by using single cell tracking. Survival analysis showed that AXL over expression correlated positively with poor overall survival of EOC in both univariate (HR=2.2 p-value=6.46e−11), and multivariate analysis (HR=1.513 p-value=0.0012). In conclusion, AXL is significantly over-expressed and displays a unique signaling pattern in the Mesenchymal subtype of EOC. Knocking down AXL in the Mesenchymal cell lines affects their EMT phenotype and migratory properties. AXL is an independent prognostic factor for EOC and is a clinically relevant target that is potentially involved in cross talks between RTK oncogenic signaling and EMT. Citation Format: Jane Antony, Tuan Zea Tan, Andrew Paterson, Chiara Recchi, Hani Gabra, Jean Paul Thiery, Ruby Yun-Ju Huang. The receptor tyrosine kinase AXL modulates oncogenic signaling and epithelial mesenchymal transition in epithelial ovarian cancer [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-BIOL-1301.

Expression and clinical significance of cortactin protein in ovarian neoplasms

To examine the expression of cortactin in epithelial ovarian cancer, and discuss the relationship between the expression of cortactin and the clinical pathology characteristics in epithelial ovarian cancer, as well as clinical significance. The expression of cortactin was detected using real-time fluorescence quantitative PCR and immunohistochemical SP method in epithelial ovarian cancer. (1) The relative content of cortactin mRNA in epithelial ovarian cancer tissue was higher than that in benign control tissue, and expression was related to histological classification and FIGO stage. (2) Cortactin protein was localized in the cytoplasm and membrane of tumor cells. The positive rate of cortactin was 73.3 % in epithelial ovarian cancer, and the rate of cortactin expression was related to histological classification. (3) The average survival period of epithelial ovarian cancer patients with positive expression of cortactin was 19.5 ± 1.2 months (95 % CI 14.6-21.4 months), compared with 34.5 ± 4.3 months in the negative expression group (95 % CI 22.1-25.9 months). Univariate survival analysis showed that: negative expression of cortactin had a significant survival advantage (χ (2) = 5.739, P = 0.017). A cox regression model for multivariate analysis revealed that cortactin was an independent prognostic factor for epithelial ovarian cancer (P = 0.001; RR = 6.452, 95 % CI 2.289-7.112). Negative expression of cortactin was an independent prognostic factor and had a survival advantage. This suggested that cells with poor differentiation showed increasing motility. Cortactin is closely related to poor prognosis.

The expression of CDK1 is associated with proliferation and can be a prognostic factor in epithelial ovarian cancer

Overexpression of cyclin-dependent kinase 1 (CDK1) has been noted to correlation with several human cancers. However, the effects of CDK1 on ovarian cancer development remain unclear. The aim of this study was to examine the effect of CDK1 and related mechanism in the proliferation and resistance to chemotherapeutic drugs of epithelial ovarian cancer (EOC). Immunohistochemical analysis was performed in 119 human ovarian cancer samples, and the data were correlated with clinicopathologic features. Furthermore, Western blot analysis was performed for CDK1 in EOC samples and cell lines to evaluate their protein levels and molecular interaction. Kaplan-Meier survival analysis showed that strong expression of CDK1 exhibited a significant correlation with poor prognosis in human EOC (P = 0.02). Meanwhile, we found that knockdown CDK1 by shCDK1 promoted the apoptosis rate and increased the sensitivity to chemotherapy drugs. Thus, CDK1 might serve as a prognostic marker, and it might be of great value for experimental therapies in EOC.

Reproductive and hormone-related risk factors for epithelial ovarian cancer by histologic pathways, invasiveness and histologic subtypes: Results from the EPIC cohort.

Whether risk factors for epithelial ovarian cancer (EOC) differ by subtype (i.e., dualistic pathway of carcinogenesis, histologic subtype) is not well understood; however, data to date suggest risk factor differences. We examined associations between reproductive and hormone-related risk factors for EOC by subtype in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 334,126 women with data on reproductive and hormone-related risk factors (follow-up: 1992-2010), 1,245 incident cases of EOC with known histology and invasiveness were identified. Data on tumor histology, grade, and invasiveness, were available from cancer registries and pathology record review. We observed significant heterogeneity by the dualistic model (i.e., type I [low grade serous or endometrioid, mucinous, clear cell, malignant Brenner] vs. type II [high grade serous or endometrioid]) for full-term pregnancy (phet = 0.02). Full-term pregnancy was more strongly inversely associated with type I than type II tumors (ever vs. never: type I: relative risk (RR) 0.47 [95% confidence interval (CI): 0.33-0.69]; type II, RR: 0.81 [0.61-1.06]). We observed no significant differences in risk in analyses by major histologic subtypes of invasive EOC (serous, mucinous, endometrioid, clear cell). None of the investigated factors were associated with borderline tumors. Established protective factors, including duration of oral contraceptive use and full term pregnancy, were consistently inversely associated with risk across histologic subtypes (e.g., ever full-term pregnancy: serous, RR: 0.73 [0.58-0.92]; mucinous, RR: 0.53 [0.30-0.95]; endometrioid, RR: 0.65 [0.40-1.06]; clear cell, RR: 0.34 [0.18-0.64]; phet = 0.16). These results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes.

May the platelet to lymphocyte ratio be a prognostic factor for epithelial ovarian cancer?

The study aimed to evaluate changes in hematologic parameters, including white blood cell, platelet count, platelet indices, the platelet to lymphocyte and neutrophil to lymphocyte ratios in patients with early and advanced stages of epithelial ovarian cancers. The study included 100 patients with epithelial ovarian cancer who underwent primary staging exploratory laparotomy. Preoperative hematologic parameters, tumor histopathologic type, grade, stage and serum CA-125 levels were retrospectively analyzed. These parameters were compared between the patients with early (stage I-II) and advanced (stage III-IV) ovarian cancer. White blood cell count and platelet indices, including mean platelet volume, platelet distribution width and platelet crit did not show a statistically significant difference between groups with early and advanced ovarian cancer. However, the neutrophil to lymphocyte ratio, platelet count, the platelet to lymphocyte ratio and CA-125 level showed a statistically significant difference between the two groups (p<0.05, p<0.01, p<0.001, p<0.01 respectively). It was found that the neutrophil to lymphocyte ratio, platelet count and the platelet to lymphocyte ratio increased with the increasing stage of ovarian cancer. Furthermore, it was seen that the platelet to lymphocyte ratio is an independent prognostic factor related to the stage of epithelial ovarian cancer.

The level of RECQL1 expression is a prognostic factor for epithelial ovarian cancer.

BackgroundThe human RECQ DNA helicase family is involved in genomic stability. Gene mutations of RECQL2, RECQL3, and RECQL4 are associated with genetic disorders and induce early aging and carcinogenesis. Although previous studies have reported that the level of RECQL1 expression is correlated with the prognosis of some of malignancies, the function of RECQL1 is not yet clarified. The present study aimed to examine the relationship between prognosis and the level of RECQL1 expression in epithelial ovarian cancer (EOC), and to identify the role of RECQL1 in EOC cells.MethodsThe level of RECQL1 expression was determined immunohistochemically in 111 patients with EOC who received initial treatment at Hirosaki University hospital between 2006 and 2011. Effects of RECQL1 on cell growth or apoptosis were examined in vitro using wild-type and OVCAR-3 cells (RECQL1(+) cells) and similar cells transfected with RECQL1 siRNA transfected (RECQL1(−) cells).ResultsThe level of RECQL1 expression was not related to histological type, clinical stage, or retroperitoneal lymph node metastasis, but the expression level was significantly higher (P = 0.002) in patients with recurrence than those without recurrence, and progression-free survival and complete response rate to chemotherapy were also improved in patients with RECQL1-low expression (n = 39) stage III/IV EOC (P = 0.02 and P <0.05 vs RECQL1-high expression patients (n = ), respectively). A cell proliferation and colony formation assays revealed significantly less growth of RECQL1(−) cells compared to RECQL1(+) cells. A flow cytometry using annexin V -FITC and propidium iodide (PI) staining revealed a significant increase in apoptotic RECQL1(−) cells. Cell cycle analysis showed a significantly greater distribution in subG1 phase indicating apoptotic cells in RECQL1(−) cells than in RECQL1(+) cells.ConclusionsThese results suggest that RECQL1 is a prognostic factor for EOC and that RECQL1 contributes to potential malignancy by inhibiting apoptosis.

Prognostic value of lymph node ratio in patients with advanced epithelial ovarian cancer

ObjectiveLymph node status is an established prognostic factor in epithelial ovarian cancer (EOC). Lymph node ratio (number of positive LN/number of resected LN) reflects both qualitative and quantitative lymph node spread as well as surgical effort and extent of disease. We evaluated whether LNR is a more precise prognostic factor than conventional lymph node status in patients with EOC. MethodsThe present retrospective study includes 809 patients with EOC, who underwent primary cytoreductive surgery between 2000–2013. Clinico-pathological parameters and survival data were extracted from a prospectively maintained tumor registry database. The optimal cut-off point for LNR was calculated by using Martingale residuals. Survival analyses were calculated using Kaplan–Meier method and Cox regression models. ResultsLymphadenectomy was performed in 693 (85.7%) out of 809 patients. Median number of removed LN was 64 (IQR 25–75%: 39–84). LNR of 0.25 was identified as the optimal prognostic cut-off value. The estimated 5-year-OS rates were 69.3% for patients with node-negative EOC compared to 33.1% for patients with any lymph node metastasis (p<0.001). The estimated 5-year-OS rates were 42.5% for patients with LNR≤0.25, and 18.0% for patients with LNR>0.25 (p<0.001). Additionally in multivariate analysis LNR>0.25 was approved to be an independent prognostic factor for overall survival (adjusted HR 1.44, 95% CI 1.04–2.00; p=0.028). ConclusionLNR more precisely predicts overall survival than conventional lymph node status in EOC patients undergoing primary debulking surgery.

Correction: The MyD88+ Phenotype Is an Adverse Prognostic Factor in Epithelial Ovarian Cancer

Correction: The MyD88+ Phenotype Is an Adverse Prognostic Factor in Epithelial Ovarian Cancer