Analysis of Erythrocyte Sedimentation Rate Order in Epithelial Ovarian Cancer.

Erythrocyte sedimentation rate order (ESRO), platelet-lymphocyte ratio (PLR), red cell distribution width (RDW), and neutrophil-lymphocyte ratio (NLR) are hematological parameters that reflect the presence of biomarkers in epithelial ovarian cancer (EOC). This study evaluated the best haematological parameter in order to distinguish between EOC patients and healthy individuals. There were a total of 33 patients with EOC as subjects treated in Dr. Sardjito hospital, Yogyakarta, Indonesia and 32 volunteer subjects as controls. Curves of receiver operation, area under the curve, specificity, and sensitivity were estimated. To demonstrate EOC's presence, the ESRO was better than the hematological parameters of RDW, PLR, and NLR (AUC = 0.9245, 0.9010, 0.8351, and 0.7457, respectively; sensitivity and specificity = 83.3 and 90.6; 88.9 and 87.5; 100.0 and 68.8; and 94.4 and 53.1, respectively) at the cut-off points 1,125, 44.2, 163.2, and 2,551. Hence, ESRO is a better parameter to indicate the presence of EOC compared to RDW, PLR and NLR.

Cytokines as Prognostic Biomarkers of Epithelial Ovarian Cancer (EOC): A Systematic Review and Meta-Analysis.

OBJECTIVES: The value of cytokines as epithelial ovarian cancer (EOC) prognostic factors has been widely investigated. This study aimed to determine the role of single cytokine as a biomarker prognosis in EOC. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of studies reporting cytokine as the prognostic predictor in EOC based on PRISMA guideline. We included English articles investigating associations of preoperative cytokines level in tissue, blood or ascites with overall survival (OS) or disease-free survival (DFS) from PUBMED and EBSCO. Summary hazard ratios (HRs) and confidence intervals (CIs) were calculated. RESULTS: Fifty studies investigating twenty types of cytokines in tumor tissue, serum, and ascites from 5,376 patients were included. Pre-operative high VEGF level was associated with poor OS (HR 2.28, 95%CI [1.28, 3.28]) and DFS (HR 2.13, 95%CI [1.63, 2.78]) in serum and OS (HR 1.80, 95%CI [1.45, 2.23]) in tissue. IL-6 level in blood was associated with DFS (HR 1.60, 95%CI [1.21, 2.11]). There was no single cytokine which investigated by at least 2 studies reporting hazard ratio in ascites, so we did not conduct the meta-analysis. Other cytokines (serum IL-8; ascites fluid IL-8, IL-10, IFN-γ, TNF-α; and ovarian tissue TGF-α, CSF-1, IL-10 ,TGF-ß1, IL-17) associated with the poorer prognosis, could not be pooled due to lack of studies. CONCLUSION: Pre-operative VEGF level in serum and tissue specimen seem to be the potential candidate of an unfavorable prognostic biomarker for EOC. The evidence was lacking to support the other cytokines investigated in blood, tissue and ascites as prognostic biomarkers for EOC.

Impact of Preoperative Serum Levels of CA 125 on Epithelial Ovarian Cancer Survival.

BACKGROUND: CA125 is very helpful in treatment monitoring and detection of epithelial ovarian cancer (EOC) recurrence. However there is controversy as to its accuracy and optimal usage. What is the impact of the CA125 levels before primary surgery treatment to the survival of patients? This study aimed to detect any association of preoperative serum levels with prognosis and survival in EOC patients. MATERIALS AND METHODS: Our cohort comprised EOC patients in Dr. Sardjito Hospital, Yogyakarta, Indonesia, who complied with follow up. To explore the effect of preoperative CA125 levels and other variables on survival Cox's regression models were applied. RESULTS: A total of 90 cases of EOC who had surgery were available for follow up. The level of CA125 poroved to be a prognostic factor for overall survival of EOC patients, with an adjusted HR of 4.10 (p = 0.03). Adjuvant chemotherapy was another prognostic factor, 1 - 2 cycles having an adjusted HR of 0.17 (p = 0.04) and 3 - 8 cycles HR 0.39 (p = 0.06). Other factors such as age of patients adjusted HR 1.54 (p = 0.32), moderate differentiation (adjusted HR 1.61, p = 0.51) poor differentiation (adjusted HR 3.41, p = 0.15), and stage of disease (adjusted HR 1.98, p = 0.27) were statistically not significant. However, this might have been because the power of the study was low. CONCLUSIONS: Preoperative level of CA125 is a prognostic factor for overall survival in EOC patients. The best cut-off for prognostic classification of CA125 serum level is 70 U/ml.

Malignancy risk scoring of hydatidiform moles.

BACKGROUND: Several risk factors leading to malignant transformation of hydatidiform moles have been described previously. Many studies showed that prophylactic chemotherapy for high risk hydatidiform moles could significantly decrease the incidence of malignancy. Thus, it is essential to discover a breakthrough to determine patients with high risk malignancy so that prophylactic chemotherapy can be started as soon as possible. OBJECTIVES: Development of a scoring system of risk factors as a predictor of hydatidiform mole malignant transformation. MATERIALS AND METHODS: This research is a case control study with hydatidiform mole and choriocarcinoma patients as subjects. Multiple logistic regression was used to analyze the data. Odds ratios (OR), attributable at risk (AR : OR-1) and risk index (ARxß) were calculated for develoipment of a scoring system of malignancy risk. The optimal cut-off point was determined using receiver operating characteristic (ROC) curve. RESULTS: This study analyzed 34 choriocarcinoma cases and 68 benign hydatidiform mole cases. Four factors significantly increased the risk of malignancy, namely age≥35 years old (OR:4.41, 95%CI:1.07- 16.09, risk index 5); gestational age≥12 weeks (OR:11.7, 95%CI:1.8-72.4, risk index 26); uterine size greater than the gestational age (OR:10.2, 95%CI:2.8-36.6, risk index 21); and histopathological grade II-III (OR:3.4, 95%CI:1.1-10.6, risk index 3). The lowest and the highest scores for the risk factors were zero and 55, respectively. The best cut-off point to decide high risk malignancy patients was ≥31. CONCLUSIONS: Malignant transformation of hydatidiform moles can be predicted using the risk scoring by analyzing the above four parameters. Score≥31 implies high risk patients so that prophylactic chemotherapy can be promptly administered for prevention.

Methylation Status and Expression of BRCA2 in Epithelial Ovarian Cancers in Indonesia.

Ovarian cancer is the main cause of mortality in gynecological malignancy and extensive studies have been conducted to study the underlying molecular mechanisms. The BRCA2 gene is known to be an important tumor suppressor in ovarian cancer, thereby BRCA2 alterations may lead to cancer progression. However, the BRCA2 gene is rarely mutated, and loss of function is suspected to be mediated by epigenetic regulation. In this study we investigated the methylation status and gene expression of BRCA2 in ovarian cancer patients. Ovarian cancer pateints (n=69) were recruited and monitored for 54 months in this prospective cohort study. Clinical specimens were used to study the in situ expression of aberrant BRCA2 proteins and the methylation status of BRCA2. These parameters were then compared with clinical parameters and overall survival rate. We found that BRCA2 methylation was found in the majority of cases (98.7%). However, the methylation status was not associated with protein level expression of BRCA2 (49.3%). Therefore in addition to DNA methylation, other epigenetic mechanisms may regulate BRCA2 expresison. Our findings may become evidence of BRCA2 inactivation mechanism through DNA methylation in the Indonesian population. More importantly, from multivariate analysis, BRCA2 expression was correlated with better overall survival (HR 0.32; p=0.05). High percentage of BRCA2 methylation and correlation of BRCA2 expression with overall survival in epithelial ovarian cancer cases may lead to development of treatment modalities specifically to target methylation of BRCA genes.

Methylation status and immunohistochemistry of BRCA1 in epithelial ovarian cancer.

BACKGROUND: Cancer initiation and progression are controlled by genetic and epigenetic events. One epigenetic process which is widely known is DNA methylation, a cause of gene silencing. If a gene is silenced the protein which it encodes will not expressed. OBJECTIVES: 1. Identify the methylation status of BRCA1 in patients with epithelial ovarian cancer (EOC)and assess BRCA1 protein expression in tumor tissue. 2. Examine whether BRCA1 gene methylation and BRCA1 protein are associated with survival of epithelial ovarian cancer patients. METHODS: The study design was a prospective-cohort study, conducted at Sardjito hospital, Yogyakarta, Indonesia. RESULTS: A total of 69 cases were analyzed in this study. The data showed that the methylation status of BRCA1 in EOC was positive in 89.9%, with clear protein expression of BRCA1 in 31.9%. Methylation status and expression of BRCA1 were not prognosticators of EOC patients. Menarche, CA125 level, clinical stage and residual tumor were independent factors for prognosis.

Combined panel of serum human tissue kallikreins and CA-125 for the detection of epithelial ovarian cancer.

OBJECTIVE: To determine the predictive accuracy of the combined panels of serum human tissue kallikreins (hKs) and CA-125 for the detection of epithelial ovarian cancer. METHODS: Serum specimens collected from 5 Indonesian centers and 1 Vietnamese center were analyzed for CA-125, hK6, and hK10 levels. A total of 375 specimens from patients presenting with ovarian tumors, which include 156 benign cysts, 172 epithelial ovarian cancers (stage I/II, n=72; stage III/IV, n=100), 36 germ cell tumors and 11 borderline tumors, were included in the study analysis. Receiver operating characteristic analysis were performed to determine the cutoffs for age, CA-125, hK6, and hK10. Sensitivity, specificity, negative, and positive predictive values were determined for various combinations of the biomarkers. RESULTS: The levels of hK6 and hK10 were significantly elevated in ovarian cancer cases compared to benign cysts. Combination of 3 markers, age/CA-125/hk6 or CA-125/hk6/hk10, showed improved specificity (100%) and positive predictive value (100%) for prediction of ovarian cancer, when compared to the performance of single markers having 80-92% specificity and 74-87% positive predictive value. Four-marker combination, age/CA-125/hK6/hK10 also showed 100% specificity and 100% positive predictive value, although it demonstrated low sensitivity (11.9%) and negative predictive value (52.8%). CONCLUSION: The combination of human tissue kallikreins and CA-125 showed potential for improving prediction of epithelial ovarian cancer in patients presenting with ovarian tumors.