Prognostic Factor In Ovarian Cancer Research Articles

A novel biomarker ARMc8 promotes the malignant progression of ovarian cancer.

Ovarian cancer is the most lethal gynecologic malignancy worldwide, and the survival rates have remained low in spite of medical advancements. More research is dedicated to the identification of novel biomarkers for this deadly disease. The association between ARMc8 and ovarian cancer remained unraveled. In this study, immunohistochemical staining was used to examine ARMc8 expression in 247 cases of ovarian cancer, 19 cases of borderline ovarian tumors, 41 cases of benign ovarian tumors, and 9 cases of normal ovarian tissues. It was shown that ARMc8 was predominantly located in the cytoplasm of tumor cells, and its expression was up-regulated in the ovarian cancer (61.9%) and the borderline ovarian tumor tissues (57.9%), in comparison with the benign ovarian tumors (12.2%; P < .05) and the normal ovarian tissues (11.1%; P < .05). In ovarian cancer, ARMc8 expression was closely related to International Federation of Gynecology and Obstetrics stages (P = .002), histology grade (P < .001), lymph node metastasis (P = .008), and poor prognosis (P < .001). Univariate and multivariate Cox analyses revealed that ARMc8 expression was an independent prognostic factor for ovarian cancer (P = .039 and P = .005). In addition, ARMc8 could promote the invasion and migration of ovarian cancer cells. Overexpressing ARMc8 enhanced the invasion and metastasis capacity of ARMc8-low Cavo-3 cells (P < .001), whereas interfering ARMc8 significantly reduced cell invasion and metastasis in ARMc8-high SK-OV-3 cells (P < .001). Furthermore, ARMc8 could up-regulate matrix metalloproteinase-7 and snail and down-regulate α-catenin, p120ctn, and E-cadherin. Collectively, ARMc8 may enhance the invasion and metastasis of ovarian cancer cells and likely to become a potential therapeutic target for ovarian cancer.

Effector CD8+ T cells abrogate fibroblasts-mediated chemoresistance in ovarian cancer (TUM2P.1007)

Abstract Tumor infiltrating effector CD8+ T cells have been described to play a major role in antitumoral activity and to be a favorable prognostic factor in ovarian cancer. The strategies of immunotherapy to improve effector T cells response have also shown potential clinical benefit in subset of ovarian cancer patients. Currently platinum-based chemotherapy is still the most active regimen for ovarian cancer treatment. However, the therapeutic resistance is a major challenge to limit the therapeutic efficiency. Here we found primary fibroblasts isolated from ovarian tumor speciman could induce resistance against cisplatin in cancer cells when the two cell types were co-cultured in vitro or co-inoculated in vivo. Activated CD8+ T cells abolished fibroblasts-mediated cisplatin resistance through IFNγ secretion. Next, we found fibroblasts induced cisplatin resistance through increasing intracellular Glutathione (GSH) level and reducing the cisplatin accumulation in cancer cells. We also identified both intact GSH and Cysteine released by fibroblasts contributed to cisplatin resistance in cancer cells. IFNγ producted by activated CD8+ T cells promoted fibroblasts extracellular GSH degradation through up-regulation of Gamma-glutamyl transpeptidase, and also diminished Cysteine generation by fibroblasts through down-regulation of System xc⁻ cystine/glutamate antiporter.These date implicate effector T cells immunotherapy as a powerful regimen to overcome the resistance to chemotherapy.

Low programmed cell death 5 expression is a prognostic factor in ovarian cancer.

Background:Ovarian cancer is a leading gynecological malignancy. We investigated the prognostic value of programmed cell death 5 (PDCD5) in patients with ovarian cancer.Methods:Expression levels of PDCD5 mRNA and protein were examined in six ovarian cancer cell lines (SKOV3, CAOV3, ES2, OV1, 3AO, and HOC1A) and one normal ovarian epithelial cell line (T29) using reverse transcription polymerase chain reaction, Western blotting, and flow cytometry. After inducing PDCD5 induction in SKOV3 cells or treating this cell line with taxol or doxorubicin (either alone or combined), apoptosis was measured by Annexin V-FITC/propidium iodide staining. Correlations between PDCD5 protein expression and pathological features, histological grade, FIGO stage, effective cytoreductive surgery, and serum cancer antigen-125 values were evaluated in patients with ovarian cancer.Results:PDCD5 mRNA and protein expression were downregulated in ovarian cancer cells. Recombinant human PDCD5 increased doxorubicin-induced apoptosis in SKOV3 cells (15.96 ± 2.07%, vs. 3.17 ± 1.45% in controls). In patients with ovarian cancer, PDCD5 expression was inversely correlated with FIGO stage, pathological grade, and patient survival (P < 0.05, R = 0.7139 for survival).Conclusions:PDCD5 expression is negatively correlated with disease progression and stage in ovarian cancer. Therefore, measuring PDCD5 expression may be a good method of determining the prognosis of ovarian cancer patients.

Microvessel density as a prognostic factor in ovarian cancer: a systematic review and meta-analysis.

The prognostic value of microvessel density (MVD), reflecting angiogenesis, detected in ovarian cancer is currently controversial. Here we performed a meta-analysis of all relevant eligible studies. A comprehensive search of online PubMed, Medline, EMBASE and Sciencedirect was performed to identify all related articles. The search strategy was designed as 'microvessel density', 'ovarian cancer', 'ovarian neoplasm', 'CD34' and 'angiogenesis'. The studies were categorized by author/year, number of patients, FIGO stage, histology, cutoff value for microvessel density, types of survival analysis, methods of hazard rations (HR) estimation, HR and its 95% confidence interval (CI). Combined hazard ratios suggested that high MVD was associated with poor overall survival (OS) and progression-free survival (PFS), with HR and 95% CIs of 1.84 (1.33-2.35) and 1.36 (1.06-1.66), respectively. Subgroup analysis showed that high MVD detected by CD34 was relevant for OS [HR=1.67 (1.36-2.35)], but not MVD detected with other antibodies [HR=2.11 (0.90-3.31)]. Another subgroup analysis indicated that high MVD in patients without pre-chemotherapy, but not with pre- chemotherapy, was associated with OS [HR=1.88(1.59-2.18 and HR=1.70 (-0.18-3.59)]. The OS and PFS with high MVD were significant poorer than with low MVD in ovarian cancer patients. However, high MVD detected by CD34 seems to be more associated with survival for patients without pre-chemotherapy.

Expression and significance of CD44, CD47 and c-met in ovarian clear cell carcinoma.

Aims: The aim of the present study is to investigate the differential expression of CD44, CD47 and c-met in ovarian clear cell carcinoma (OCCC), the correlation in their expression and their relationship with the biological behavior of OCCC. Methods: We used immunohistochemistry to examine the expression of CD44, CD47 and c-met in OCCC (86 cases) and investigated the effects of the expression and interaction of these molecules on the development of OCCC. Results: CD44, CD47 and c-met expression was significantly high in OCCC. Expression of CD44 and CD47 correlated with patient surgical stage, chemotherapy resistance and prognosis (all p < 0.05), and expression of c-met correlated with chemotherapy resistance and prognosis (all p < 0.05), but did not correlate with lymph node metastasis (all p > 0.05). The surgical stage, CD44, CD47 and c-met expression were independent risk factors for OCCC prognosis (all p < 0.05). Patients with low levels of CD44, CD47 and c-met showed better survival than those with high levels (all p < 0.05). There was a positive correlation between CD44 (or CD47) and c-met, as well as between CD44 and CD47 (the Spearman correlation coefficient rs was 0.783, 0.776 and 0.835, respectively, all p < 0.01). Additionally, pairwise correlation analysis of these three markers shows that the high expression of CD44/CD47, CD44/c-met and CD47/c-met were correlated with patient surgical stage, chemotherapy resistance and prognosis (all p < 0.05), but did not correlate with lymph node metastasis (all p > 0.05). Conclusions: Expression of CD44, CD47 and c-met was upregulated in OCCC and pairwise correlation. CD44, CD47 and c-met may have synergistic effects on the development of OCCC and are prognostic factors for ovarian cancer.

Survival outcome in endometrial cancer patients according to hereditary predisposition

ObjectiveA familial history of ovarian cancer/breast cancer is considered a significant prognostic factor for ovarian cancer. We investigated hereditary factors by examining the incidence of synchronous malignancy in patients with endometrial cancer, and assessed the prognostic role of heredity in endometrial cancer. MethodsWe retrospectively evaluated patients with endometrial cancer who underwent surgery from January 2001 to April 2011. A hereditary background in this study was defined as double primary cancer, that is, endometrial cancer accompanied by colon, ovarian, or breast cancer suggestive of Lynch syndrome, hereditary breast ovarian cancer syndrome, or Cowden syndrome, respectively. ResultsAmong 282 patients with endometrial cancer in the study population, 20 patients (7.1%) had a hereditary predisposition: 10 patients (3.5%) had ovarian cancer, six patients (2.1%) had breast cancer, and four patients (1.4%) had colon cancer. Age and lower uterine segment involvement were not statistically different between the hereditary and nonhereditary groups. The majority of the women in the hereditary group presented with Stage I cancer; however, there were no significant differences in Stage I cancer between the hereditary group and the sporadic endometrial cancer group (85% and 77%, respectively, p = 0.561). The median follow-up period was 60 months. A 5-year overall survival rate was not different between the two groups (95% and 95%, respectively, p = 0.659). Among a subgroup of patients with Stage I endometrial cancer, the 5-year overall survival rate was lower in the endometrial cancer with a hereditary predisposition group compared with the sporadic endometrial cancer group (94% and 98%, respectively, p = 0.027). ConclusionSeven percent of the women with endometrial cancer in our study had other malignancies such as ovarian, colon, or breast cancer synchronously. Among a subgroup of patients with Stage I cancer in the endometrial cancer with a hereditary predisposition group, the 5-year overall survival rate was significantly lower (94%). This finding should be confirmed in a larger population.

Assessment of selected cytokines, proteins, and growth factors in the peritoneal fluid of patients with ovarian cancer and benign gynecological conditions.

ObjectivesThe ovarian tumor microenvironment, ie, the peritoneal fluid, is an intriguing research subject. The goal of this study was to assess the behavior of selected cytokines and growth factors within the peritoneal fluid in pathologies associated with ascites and to assess the relationship between the levels of these substances and select prognostic factors of ovarian cancer.MethodsA total of 74 patients were enrolled in the study, including 36 patients with ovarian cancer and 38 patients with benign gynecological conditions. Peritoneal fluid collected during surgical procedures was used to assess the levels of interleukin (IL)-6, IL-8, stem cell factor (SCF), dickkopf-1, growth differentiation factor-15 (GDF-15), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), osteoprotegerin (OPG), osteopontin, osteonectin, and human epididymis protein 4. The median levels of these factors were compared between the two groups, and the levels of selected factors were assessed in the ovarian cancer group with regard to the clinical stage of cancer, tumor differentiation, presence of peritoneal spread and positive peritoneal fluid cytology results. The diagnostic value of the analyzed proteins within the peritoneal fluid was also assessed.ResultsDifferences were observed between the patients with ovarian cancer and the patients with benign gynecological conditions associated with ascites with regard to the levels of IL-6, IL-8, GDF-15, SCF, osteopontin, osteonectin, and OPG. There were no differences in dickkopf-1, TRAIL, and human epididymis protein 4 levels between the two study groups. Cancer stage affected only the mean SCF and OPG levels, with lower SCF values and higher OPG values in advanced cancers compared to less-advanced cancers. Tumor differentiation was associated with significantly lower SCF values in the group of poorly differentiated tumors. A significant reduction in SCF values and a significant increase in OPG and IL-6 values were also observed within cancer cell-positive peritoneal fluid. Peritoneal spread was associated with higher levels of TRAIL, osteonectin, and IL-6 in ovarian cancer patients.ConclusionOn the basis of the conducted studies, it appears that of the studied factors, GDF-15, SCF, and OPG deserve special attention in the context of future research on the tumor microenvironment. With regard to diagnostics, attention should be given primarily to GDF-15, IL-6, and osteonectin.

Étude de la qualité de vie dans les néoplasies ovariennes : outils et enjeux

Health-related quality of life (QoL) in patients treated for ovarian cancer is directly and heavily impacted by the natural history of cancer, its evolution and its therapeutic modalities. The evaluation and consideration of various parameters of QoL seems to be a major issue. Indeed, on the one hand, it is essential to take into account the opinion of patients in the choice of therapeutic strategies for this cancer with a poor prognosis and, on the other hand, more and more studies show that QoL is an independent prognostic factor in ovarian cancer. Improvement in this case, in addition to being an endpoint by itself, would potentially improve the overall survival of patients. To date there are several tools to assess QOL of patients with ovarian cancer. The 2 questionnaires most commonly used are: FACT-O and the EORTC QLQ-OV28. The aim of our study was to evaluate from a review of the literature, the reciprocal effects of ovarian cancer on QoL and QoL on ovarian cancer survival, as well as specificities of each of the 2 questionnaires most commonly used in assessing the QoL.

The association between endometriosis and survival outcomes of ovarian cancer: Evidence-based on a meta-analysis.

Although it is generally recognized that endometriosis was significantly associated with higher risk of ovarian cancer, the association between endometriosis and the cancer survival outcomes is still not clear. This meta-analysis aims to pool previous studies and to make an update estimate. Relevant studies were searched among PubMed, Medline and Embase. Hazard ratio (HR) and the corresponding 95% confidence intervals (CI) of progression-free survival (PFS) and overall survival (OS) were pooled with generic inverse variance method. The proportion of the low stage and grade tumors (stage: Stage I and II among total; grade: Grade I among total) in endometriosis-associated ovarian cancer (EAOC) group and in non-EAOC group were assessed with odd ratio and the corresponding 95% CI. Endometriosis-associated ovarian cancer were significantly associated with higher rate of OS in crude analysis (HR: 0.74, 95% CI: 0.63-0.87, P = 0.0003). However, in most of the studies included, the OS benefit was not significant under multivariable survival analysis. EAOC patients generally had early-stage, low histological grade tumors and younger age compared with non-EAOC patients. No difference was observed in PFS between the two groups. The OS benefits associated with endometriosis might be closely related to higher prevalence of patients diagnosed at early-stage and greater chance of receiving optimal cytoreductive surgery or chemotherapy. Endometriosis should not be viewed as an independent prognostic factor of ovarian cancer.

High levels of KAP1 expression are associated with aggressive clinical features in ovarian cancer.

KAP1 is an universal corepressor for Kruppel-associated box zinc finger proteins in both normal and tumor cells. In this study, the biological function and clinical significance of KAP1 expression in ovarian cancer were investigated. Immunohistological staining of KAP1 was evaluated in 111 patients with ovarian epithelial cancer, 15 with ovarian borderline tumor, and 20 normal ovarian tissue. The correlations of KAP1 expression with clinicopathological features were studied. Kaplan-Meier analysis and Cox proportional hazard modeling were used to assess overall survival to analyze the effect of KAP1 expression on the prognosis of ovarian cancer. The positive rates of KAP1 were significantly higher in ovarian epithelial cancer (55.7%) and borderline tumor (20.0%) than in normal ovarian tissue (5.0%) (all p < 0.01). KAP1 expression correlated significantly with clinical stage (χ2 = 14.57, p < 0.0001), pathological grade (χ2 = 6.06, p = 0.048) and metastases (χ2 =10.38, p = 0.001). Patients with high KAP 1 levels showed poor survival (p < 0.0001). Multivariate analysis showed that KAP1 high expression was an independent predictor for ovarian cancer patients (hazard ratio = 0.463; 95% confidence interval = 0.230–0.9318, p = 0.031). Functionally, depletion of KAP1 by siRNA inhibited ovarian cancer cell proliferation, cell migration. KAP1 expression correlated with aggressive clinical features in ovarian cancer. High KAP1 expression was a prognostic factor of ovarian cancer.

Overexpression of forkhead box protein M1 (FOXM1) in ovarian cancer correlates with poor patient survival and contributes to paclitaxel resistance.

AimDeregulation of FOXM1 has been documented in various cancers. The aim of this study was to evaluate the role of FOXM1 in ovarian cancer tumorigenesis and paclitaxel resistance.Experimental DesignExpression of FOXM1 was examined in 119 clinical samples by immunohistochemistry and correlated with clinicopathological parameters. Effects of FOXM1 knockdown on ovarian cancer cell migration, invasion and mitotic catastrophe were also studied. qPCR and ChIP-qPCR were used to establish KIF2C as a novel FOXM1 target gene implicated in chemoresistance.ResultsHigh nuclear FOXM1 expression in ovarian cancer patient samples was significantly associated with advanced stages (P = 0.035), shorter overall (P = 0.019) and disease-free (P = 0.014) survival. Multivariate analysis confirmed FOXM1 expression as an independent prognostic factor for ovarian cancer. FOXM1 knockdown significantly inhibited migration and invasion of ovarian cancer cells and enhanced paclitaxel-mediated cell death and mitotic catastrophe in a p53-independent manner. Bioinformatics analysis suggested a number of potential transcription targets of FOXM1. One of the potential targets, KIF2C, exhibited similar expression pattern to FOXM1 in chemosensitive and chemoresistant cells in response to paclitaxel treatment. FOXM1 could be detected at the promoter of KIF2C and FOXM1 silencing significantly down-regulated KIF2C.ConclusionOur findings suggest that FOXM1 is associated with poor patient outcome and contributes to paclitaxel resistance by blocking mitotic catastrophe. KIF2C is identified as a novel FOXM1 transcriptional target that may be implicated in the acquisition of chemoresistance. FOXM1 should be further investigated as a potential prognostic marker and therapeutic target for ovarian cancer.

OVSCORE - a validated score to identify ovarian cancer patients not suitable for primary surgery.

Following primary debulking surgery, the presence of a residual tumor mass is one of the most important prognostic factors in ovarian cancer. In a previous study, we established the OVSCORE, an algorithm to predict surgical outcome, based on the clinical factors of nuclear grading and ascitic fluid volume, plus the cancer biomarkers, kallikrein-related peptidases (KLKs), KLK6 and KLK13. In the present study, OVSCORE performance was tested in an independent ovarian cancer patient cohort consisting of 87 patients. The impact of KLKs, KLK5, 6, 7 and 13 and other clinical factors on patient prognosis and outcome was also evaluated. The OVSCORE proved to be a strong and statistically significant predictor of surgical success in terms of area under the receiver operating characteristic curve (ROC AUC, 0.777), as well as positive and negative predictive value in this independent study group. KLK6 and 13 individually did not show clinical relevance in this cohort, but two other KLKs, KLK5 and KLK7, were associated with advanced FIGO stage, higher nuclear grade and positive lymph node status. In the multivariate Cox regression analysis for overall survival (OS), KLK7 had a protective impact on OS. This study confirms the role of KLKs in ovarian cancer for surgical success and survival, and validates the novel OVSCORE algorithm in an independent collective. As a key clinical application, the OVSCORE could aid gynecological oncologists in identifying those ovarian cancer patients unlikely to benefit from radical surgery who could be candidates for alternative therapeutic approaches.

Current status of ovarian cancer in the Spanish Province of Castellon. Prognostic factors in observed and relative survival. A population cancer-registry-based study between 2004 and 2008

Abstract Background The aim of this population-based study was to assess independent prognostic factors in ovarian cancer by analyzing observed and relative survival in a representative Spanish population. Methods We carried out a retrospective, observational, population-registry-based study. Data on 207 patients with ovarian cancer were provided by the Castellon Cancer Registry. Observed and relative survival were described at 1, 3 and 5 years. The effect of prognostic factors on survival was assessed with univariate and multivariate analyses. Results The median follow-up was 40.8 months (range: 12–108 months). Observed and relative survival rates at 1, 3 and 5 years were 79%, 51%, 33%, and 84%, 58%, 40%, respectively. Age older than 70 years showed worse observed survival in the univariate and multivariate analyses. Only FIGO stage was an independent prognostic factor for observed and relative survival. Conclusions Survival is poor in patients with ovarian cancer. In our population-registry-based study, only age at diagnosis and FIGO stage were independent prognostic factors for observed survival, whereas only FIGO stage could be considered a prognostic factor for relative survival.

NIS Mediates Iodide Uptake in the Female Reproductive Tract and Is a Poor Prognostic Factor in Ovarian Cancer

The sodium iodide symporter (NIS) mediates active transport of iodide into the thyroid and the lactating mammary glands and is highly expressed in thyroid and breast carcinomas. NIS is clinically very relevant because it allows the treatment with radioiodine of thyroid cancer patients. In this study we wanted to explore whether NIS is expressed in the ovary and in ovarian cancer. Methods included NIS and paired box 8 expression and function in ovarian cancer patients and rats by immunochemistry, immunoblot, RT-PCR, and iodide uptake. Here we demonstrate for the first time that NIS is expressed in the ovary and fallopian tube and actively accumulates significant levels of radioiodide in vivo. In a large survey of menstruating women receiving radioiodide for medical purposes, 15% showed significant uptake in the normal reproductive tract. Ovarian NIS activity is influenced by the estrous cycle stage in rats, being up-regulated during peak levels of estrogens occurring immediately before the ovulation. We unveil that the regulatory mechanism underlying this phenomenon is based on the functional cooperation of estrogen receptor-α and paired box 8. We also show that NIS is highly expressed in ovarian cancer, predicting a poor prognosis in these patients. These results provide the basis that will help minimize the impact of therapeutic doses of radioiodide on gonadal function. We also suggest that NIS is a new ovarian cancer marker, opening a door for the use of radioiodide in the diagnosis and treatment of ovarian cancer patients.

Beclin 1 Expression in Ovarian Tissues and Its Effects on Ovarian Cancer Prognosis

Beclin 1 is an autophagy-associated protein involved in apoptosis and drug resistance, as well as various malignancies. We investigated the expression of Beclin 1 protein in ovarian epithelial tissues and correlated it with the prognosis of ovarian cancer. Beclin 1 protein expression was determined using immunohistochemistry in 148 patients with ovarian epithelial cancer, 26 with ovarian borderline tumor, 25 with benign ovarian tumor, and 30 with normal ovarian tissue. The relationships between Beclin 1 protein expression and ovarian cancer pathological characteristics were analyzed. The risk factors for ovarian cancer prognosis were analyzed using Cox’s regression model. A survival curve was plotted from the follow-up data of 93 patients with ovarian cancer to analyze the effects of Beclin 1 expression on the prognosis of ovarian cancer. The positive rates of Beclin 1 were significantly higher in ovarian epithelial cancer (148) and borderline tumor (26) than in benign ovarian tumor (25) or normal ovarian tissue (30) (all p < 0.001). The surgical stage and Beclin 1 expression were both independent risk factors for ovarian cancer prognosis (both p < 0.05). Patients with high Beclin 1 levels showed better survival than those with low Beclin 1 levels (p = 0.009). Beclin 1 protein is upregulated in ovarian epithelial cancer and is a prognostic factor of ovarian cancer.

Correlation of cytokines and inducible nitric oxide synthase expression with prognostic factors in ovarian cancer

The study related the immunohistochemical staining of cytokines (IL2, IL5, IL6, IL8, IL10, and TNF-alpha), and iNOS staining with clinical and pathological parameters of patients with primary ovarian malignancy. We prospectively evaluated 40 patients who underwent surgical treatment in accordance with pre-established criteria and later confirmed diagnosis of ovarian cancer. Immunohistochemistry study for cytokines (IL2, IL5, IL6, IL8, IL10, TNF-alpha) and iNOS was performed. The evaluation of prognostic factors was performed using the Fisher's exact test. The significance level was less than 0.05. Histological grade 1 was significantly correlated with strong intensity for TNF-α (p=0.0028). In addition, early stages showed strong expression intensity of TNF-α, but this was at the limit of significance (p=0.0525). Strong staining immunohistochemical IL5 was related to disease-free survival less than or equal to 24 months, suggesting that a factor of poor prognosis, but there was no statistical significance (p=0.1771). There was no statistical significance in relation at other cytokines studied. Therefore, immunohistochemical staining in strong intensity for TNF-α was related to histological grade 1 and early stages of ovarian cancer in our sample of patients.

Overexpression of cysteine cathepsin L is a marker of invasion and metastasis in ovarian cancer

Cysteine cathepsins (CTSs) are involved in the degradation and remodeling of the extracellular matrix and are associated with cellular transformation, differentiation, motility and adhesion in cancer development. Previous studies indicate that CTSs may be involved in ovarian cancer invasion and metastasis. However, due to the lack of large sample clinical studies and direct experimental evidence for the relationship between the expression of CTSs and invasion and metastasis, the diagnostic and prognostic value of CTSs in ovarian cancer progression has not been elucidated. In the present study, we observed that expression levels of CTSB, CTSL and CC in malignant ovarian tumors were significantly higher than the expression levels in benign tumors and normal ovarian tissues, yet their associations with clinicopathological features varied. In particular, CTSL was related to lymph node metastasis, CC was related to liver metastasis and omental metastasis, and CTSB and CTSL expression levels were found to be independent prognostic factors in ovarian cancer. Further study indicated that the serum level of CTSL was significantly higher in patients with ovarian malignant tumors than the levels in benign tumors and healthy controls, and the levels were elevated in low grade and advanced stage compared to the levels in high grade and early stage disease, suggesting that the serum level of CTSL may be a useful serum marker for the diagnosis of ovarian cancer. Furthermore, the expression of CTSL in ovarian cancer cells can greatly enhance the ability of cell invasion and metastasis, although no change was observed for cell adhesion. Taken together, we demonstrated that the overexpression of CTSL is involved in tumor invasion and metastasis, and the CTSL level in serum may be a marker for invasion and metastasis in ovarian cancer.

Significance of blood serum catalase activity and malondialdehyde level for survival prognosis of ovarian cancer patients

Background and objectiveSeveral markers were found to be potential prognostic factors in ovarian cancer. Among markers resembling systemic changes in the host's organism are markers of the oxidative stress. In this study we attempted to analyze the oxidant and antioxidant parameters of ovarian cancer patients. Materials and methodsA total of 42 patients with newly diagnosed stages I–IV primary ovary cancer were examined. Level of malondialdehyde (MDA) and catalytic activity catalase (CAT) were determined spectrophotometrically. ResultsSignificantly lower CAT (28.2±15.5 vs. 36.1±14.6nmol/L/min, P=0.019) activity and higher MDA levels (8.7±3.0 vs. 6.7±2.7nmol/L, P=0.002) were observed in cancer patients compared with healthy volunteers. Both variables were not confirmed as prognostic factors according to Kaplan–Meier survival estimates. ConclusionsMDA and CAT demonstrate oxidative stress in cancer patients: CAT activity was significantly lower and MDA levels higher in cancer patients compared to healthy controls. These variables were not confirmed to be prognostic factors in ovarian cancer, possibly due to small size of the study group.

Decreased ARID1A expression is correlated with chemoresistance in epithelial ovarian cancer

ObjectiveLoss of ARID1A is related to oncogenic transformation of ovarian clear cell adenocarcinoma. The present study was conducted in epithelial ovarian cancer of all tissue types to investigate whether an increased or decreased expression level of ARID1A can be a prognostic factor for ovarian cancer or can influence the sensitivity to anticancer drugs.MethodsThe expression level of ARID1A was investigated in 111 patients with epithelial ovarian cancer who received initial treatment at the Hirosaki University Hospital between 2006 and 2011. The expression level of ARID1A was immunohistochemically graded using staining scores, which were calculated by multiplying the staining intensity of the nuclei by the stain-positive area.ResultsThe level of ARID1A was significantly lower in clear cell adenocarcinoma than in other histologic types. Among the patients with stage III, IV cancer (n=46), the level of ARID1A was significantly lower (p=0.026) in patients who did not achieve complete response (CR; n=12) than in patients who achieved CR (n=34). The level of ARID1A was relatively lower (p=0.07) in patients who relapsed after achieving CR (n=21) than in patients who did not relapse (n=13). When the staining score of 0 was defined as ARID1A-negative and other staining scores were defined as ARID1A-positive, there was significant difference in progression-free survival between ARID1A-negative (n=11) and ARID1A-positive (n=35) patients in stage III, IV disease.ConclusionThe result suggests that decreased ARID1A expression is correlated with chemoresistance and may be a predictive factor for the risk of relapse of advanced cancer after achieving CR.

Prognostic role of early versus late onset of bone metastasis in patients with carcinoma of the ovary, peritoneum and fallopian tube

BackgroundBone metastases are a rare manifestation in the management of ovarian cancer and thought to be associated with a poor prognosis as sign of distant spread. Only few data exist on this rare condition. The present study aimed to more information on this very distinct patient collective. Patients and methodsA retrospective chart review was carried out including all patients who had been treated from 1994 to 2009 for histologically confirmed ovarian, peritoneal and fallopian tube cancer. Overall, 1717 cases were detected and screened. Patients with bone metastasis were identified and analyzed regarding survival as well as various clinical variables. ResultsA total of 26 women who had been diagnosed with bone metastases ante mortem could be identified, resulting in an incidence of 1.50%. The majority of patients presented multiple bone lesions (80.8%) and bone spread was symptomatic in 62.5% of the cases. Mean overall survival from primary diagnosis of EOC was 50.5 months (range: 2.5–142.5 months). Median overall survival after diagnosis of bone metastases was 7.2 months. When divided into two subsets depending on timepoint diagnosis of bone metastases, there was a significant difference in overall survival. The mean overall survival from primary diagnosis of EOC in the early-onset group (n = 8), defined as occurence of bone manifestation within 12 months, was 11.2 months. The mean overall survival in the late-onset group (n = 15) was 78.4 months (P = 0.000001). ConclusionsThe time interval from diagnosis to appearance of bone metastases is a prognostic factor in ovarian cancer. While early onset bone spread has a strong negative prognostic impact, late-onset bone diagnosis of bone metastases hardly influences the prognosis at all. This finding should be considered in the management of patients with bone metastases from ovarian cancer.