PURPOSE: To determine the most powerful cancer antigen 125 (CA125)-related prognostic factor for advanced epithelial ovarian cancer (EOC) and to identify cut-off values that distinguish patients with a poor prognosis from those with a good prognosis. MATERIALS AND METHODS: We included 223 patients who received staging laparotomy and were diagnosed with stage IIC-IV serous EOC. Cox regression analysis was used to determine the most significant prognostic factor among the following variables: serum CA125 before surgery and after the first, second, and sixth cycles of chemotherapy; the nadir CA125 value; the relative percentage change in CA125 levels after the first and second cycles of chemotherapy compared to baseline CA125; CA125 half-life; time to nadir; and time to normalization of the CA125 level. RESULTS: The CA125 level after the first chemotherapy cycle was the most significant independent prognostic factor for overall survival (OS). Time to normalization (p=0.028) and relative percentage change between CA125 levels at baseline and after the first chemotherapy cycle (p=0.021) were additional independent prognostic factors in terms of OS. The CA125 level after the first chemotherapy cycle (p=0.001) and time to normalization (p<0.001) were identified as independent prognostic factors for progression free survival (PFS). CONCLUSION: Among well-established CA125-related prognostic factors, serum CA125 levels after the first cycle of chemotherapy and time to normalization were the most significant prognostic factors for both OS and PFS.
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/*therapeutic use ; CA-125 Antigen/*blood/metabolism ; Disease-Free Survival ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Neoplasms, Glandular and Epithelial/*blood/*drug therapy/mortality ; Ovarian Neoplasms/*blood/*drug therapy/mortality ; Prognosis ; Regression Analysis

OBJECTIVETo study the expression of P53 protein in the advanced ovarian serous adenocarcinoma and explore its potential correlation with the clinicopathological features and prognosis of ovarian cancer.

METHODSThe immunohistochemical staining was used to detect the expression of P53 protein in 183 patients with advanced ovarian serous adenocarcinoma. The correlation of P53 protein with the clinicopathological features and its significance in the assessment of prognosis were explored.

RESULTSThe P53 protein expression was positive in 62.8% of the patients. Chi-square test showed that the overexpression of P53 protein was positively correlated with the elevation of serum CA125 and the two-tier grading of ovarian serous adenocarcinoma (P<0.001, P=0.038). Univariate analysis suggested that the prognosis of patients was associated with two-tier grading (P=0.007), lymph node metastasis (P=0.036), preoperative serum CA125 level (P=0.002), and P53 overexpression (P<0.001). Multivariate analysis showed that the International Federation of Gynecology and Obstetrics stage (P=0.038), lymph node metastasis (P=0.002), and overexpression of P53 (P=0.001) were independent prognostic factors.

CONCLUSIONThe P53 protein expression is closely related to the prognosis of advanced ovarian serous adenocarcinoma and can be used as an important indicator for predicting the prognosis.

CA-125 Antigen ; blood ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Membrane Proteins ; blood ; Neoplasm Grading ; Neoplasm Staging ; Neoplasms, Glandular and Epithelial ; metabolism ; pathology ; Ovarian Neoplasms ; metabolism ; pathology ; Prognosis ; Tumor Suppressor Protein p53 ; metabolism

This study is a multi-center clinical study, which aimed to compare CA125, HE4, and risk of ovarian malignancy algorithm (ROMA) in predicting epithelial ovarian cancer of Korean women with a pelvic mass. Prospectively, serum from 90 Korean women with ovarian mass was obtained prior to surgery. For control group, serum from 79 normal populations without ovarian mass was also obtained. The HE4 and CA125 data were registered and evaluated separately and ROMA was calculated for each sample. Total 67 benign tumors and 23 ovarian cancers were evaluated. Median serum levels of HE4 and CA125, and ROMA score were significantly higher in patients with ovarian cancer than those with benign ovarian tumor and normal population (P < 0.001). In ROC curve analysis for women with a pelvic mass, area under the curve (AUC) for HE4 and ROMA was higher than CA125. Statistical differences in each study compared to CA125 were marginal (P compared to CA125; 0.082 for HE4 and 0.069 for ROMA). Sub-analysis revealed that AUC for HE4 and ROMA was higher than AUC for CA125 in post-menopausal women with a pelvic mass, but there were no statistically significant differences (P compared to CA125; 0.160 for HE4 and 0.127 for ROMA). Our data suggested that both HE4 and ROMA score showed better performance than CA125 for the detection of ovarian cancer in women with a pelvic mass. HE4 and ROMA can be a useful independent diagnostic marker for epithelial ovarian cancer in Korean women.
Algorithms ; Area Under Curve ; Biomarkers, Tumor/blood ; CA-125 Antigen/*blood ; Case-Control Studies ; Female ; Humans ; Middle Aged ; Neoplasms, Glandular and Epithelial/*blood/*diagnosis ; Ovarian Neoplasms/*blood/*diagnosis ; Predictive Value of Tests ; Prospective Studies ; Proteins/*metabolism ; ROC Curve ; Reference Values ; Republic of Korea

A variety of biomarkers have been identified in recent prospective and retrospective reports as being potentially predictive of venous thromboembolis (VTE), particularly idiopathic deep venous thrombosis (IDVT). This study identified a serum tumor biomarker for early screening of IDVT. A total of 128 IDVT patients (54 females and 74 males; average age: 50.9±17.4 years) were included. Carcinoembryonic antigen (CEA), ferritin, β2-microglobulin, cancer antigen (CA) 125, CA 15-3, CA 19-9, squamous cell carcinoma antigen (SCC), alpha-fetoprotein (AFP), prostate specific antigen (PSA), free PSA (f-PSA), and beta-human chorionic gonadotropin (β-HCG) in patients with IDVT were detected. Malignancies were histo- or cytopathologically confirmed. Of the 128 IDVT patients, 16 (12.5%) were found to have malignancies. Serum CEA, CA 125, CA 15-3, and CA 19-9 were found to be helpful for detecting malignancies in IDVT patients. Our study revealed a positive association between these markers and tumors in IDVT patients. On the other hand, SCC and AFP were not sensitive enough to be markers for detecting tumors in patients with IDVT. No significant differences were found in positive rates of ferritin and β2-microglobulin between tumor and non-tumor groups, and no significant difference exists in serum levels of ferritin and β2-microglobulin between the two groups. Carbohydrate antigens, CA 15-3 in particular, may be useful for differential diagnosis and prediction of malignancies in patients with IDVT.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, Neoplasm ; blood ; Antigens, Tumor-Associated, Carbohydrate ; blood ; Biomarkers, Tumor ; blood ; CA-125 Antigen ; blood ; CA-19-9 Antigen ; blood ; Carcinoembryonic Antigen ; blood ; Chorionic Gonadotropin, beta Subunit, Human ; Female ; Humans ; Male ; Middle Aged ; Mucin-1 ; blood ; Neoplasms ; blood ; complications ; diagnosis ; Prostate-Specific Antigen ; blood ; Retrospective Studies ; Sensitivity and Specificity ; Serpins ; blood ; Venous Thrombosis ; blood ; complications ; Young Adult ; alpha-Fetoproteins ; metabolism

OBJECTIVETo study the effect of Compound Ezhu Powder (CEP) on serum levels of CA125 and CA19-9, and the expression of cyclin D protein in endometriosis patients, thus providing theoretical evidence for clinical application of CEP.

METHODSTotally 69 all endometriosis patients underwent surgical treatment at Department of Gynecology and Obstetrics, Tianjin Nankai Hospital from January 2011 to January 2013 were randomly assigned to group A (35 cases) and group B (34 cases). Meanwhile, 30 patients with uterine fibroids who prepared for surgical treatment during the same period were recruited as the control group. Patients in group A took EZP 3 months before surgery. No treatment was given to patients in group B and the control group. The serum CA125 level and the expression of cyclin D in the ectopic endometrium and the eutopic endometrium were detected in the 3 groups before surgery.

RESULTSThe expression of cyclin D was higher in group A and group B than in the control group (P < 0.05). The serum levels of CA125 and CA19-9 were significantly lower in group A than in group B (P < 0.05). The expression of cyclin D in the ectopic endometrium was lower in group A than in group B, but with no statistical difference (P > 0.05). The expression of cyclin D in the eutopic endometrium was significantly lower in group A than in group B with statistical difference (P < 0.05). Meanwhile, the serum CA125 level was positively correlated with the serum CA19-9 level (r = 0.45, P < 0.05).

CONCLUSIONSThe expression of cyclin D obviously increased in endometriosis patients, which was associated with the occurrence of endometriosis. CEP could lower serum levels of CA125 and CA19-9, and down-regulate the expression level of cyclin D, indicating its roles in inhibiting the cell cycle.

Adult ; Antigens, Tumor-Associated, Carbohydrate ; blood ; CA-125 Antigen ; blood ; CA-19-9 Antigen ; blood ; Cyclin D1 ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Endometriosis ; blood ; drug therapy ; Female ; Humans

OBJECTIVE: The purpose of this study was to evaluate the expression of epidermal growth factor-like domain 7 (EGFL7) in epithelial ovarian cancer, and to assess its relevance to clinicopathological characteristics and patients' survival. METHODS: A total of 177 patients with epithelial ovarian cancer were enrolled in the current study. For each patient, a retrospective review of medical records was conducted. Immunohistochemical staining for EGFL7 was performed using tissue microarrays made with paraffin-embedded tissue block. EGFL7 expression levels were graded on a grade of 0 to 3 based on the percentage of positive cancer cells. We analyzed the correlations between the expression of EGFL7 and various clinical parameters, and also analyzed the survival outcome according to the EGFL7 expression. RESULTS: The expression of EGFL7 in ovarian cancer tissues was observed in 98 patients (55.4%). High expression of EGFL7 (grade 2 or 3) was significantly correlated with pathologic type, differentiation, stage, residual tumor after debulking surgery, lymphovascular space involvement, lymph node metastasis, high cancer antigen 125, peritoneal cytology, and ascites. Among these clinicopathologic factors, differentiation was significantly correlated with EGFL7 expression in multivariate analysis (p<0.05). Survival analysis showed that the patients with high EGFL7 expression had a poorer disease free survival than those with low EGFL7 expression (p=0.002). CONCLUSION: Our data suggest that EGFL7 expression is a novel predictive factor for the clinical progression of epithelial ovarian cancer, and may constitute a therapeutic target for antiangiogenesis therapy in patients with epithelial ovarian cancer.
Adult ; CA-125 Antigen/blood ; Cell Differentiation/physiology ; Endothelial Growth Factors/*metabolism ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Proteins/metabolism ; Neoplasm Staging ; Neoplasm, Residual ; Neoplasms, Glandular and Epithelial/*diagnosis/pathology/surgery ; Ovarian Neoplasms/*diagnosis/pathology/surgery ; Prognosis ; Retrospective Studies ; Survival Analysis ; Tumor Markers, Biological/*metabolism

OBJECTIVETo evaluate the expression of BRCA1, ERCC1, TUBB3 and PRR13 mRNA and their relationship with clinical chemosensitivity in primary ovarian cancer, and to assess the predictive value of joint detection of both BRCA1 and ERCC1 genes for the treatment of primary ovarian cancer.

METHODSPrimary epithelial ovarian tumor samples were collected from 46 patients who underwent cytoreductive surgery. Real-time quantitative PCR was used to analyze the relative expression of BRCA1, ERCC1, TUBB3 and PRR13 mRNA in those cases. The correlation of clinical chemosensitivity and the test results was statistically analyzed. The efficacy of the joint prediction of clinical chemosensitivity by combining the two drug resistance gene detection was evaluated.

RESULTSThe BRCA1 mRNA relative expression logarithm in the clinical-resistant group was 0.673±2.143, and clinical-sensitive group -1.436±2.594 (P=0.008). The ERCC1 mRNA relative expression logarithm in the clinical-resistant group was -0.529±1.982 and clinical-sensitive group -3.188±2.601 (P=0.001). BRCA1 and ERCC1 expression level is negatively correlated with platinum-based chemosensitivity. The PRR13 expressions in the two groups were not significantly different (P=0.074), and the TUBB3 expressions between the two groups were also not significantly different (P=0.619). When the intercept point value BRCA1 mRNA expression logarithm was -0.6, the predictive sensitivity, specificity, positive predictive value and negative predictive value were 73.3%, 75.0%, 84.6% and 60.0%, respectively, with the best comprehensive assessment. When the intercept point value of ERCC1 mRNA expression logarithm was -1, the predictive sensitivity, specificity, positive predictive value and negative predictive value were 80.0%, 68.8%, 82.8% and 64.7%, respectively, with the best comprehensive assessment. The combination detection of BRCA1 and ERCC1 can improve the chemotherapeutic sensitivity, specificity, positive predictive value and negative predictive value to 86.7%, 68.8%, 83.9% and 73.3%, respectively.

CONCLUSIONSBRCA1 and ERCC1 mRNA expression has a negative correlation with the clinical sensitivity of platinum-based chemotherapy. Combination detection of the two drug-resistance associated genes can improve the predictive efficacy of ovarian cancer chemosensitivity and beneficial to individual treatment of ovarian cancer.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; BRCA1 Protein ; genetics ; metabolism ; CA-125 Antigen ; blood ; Carboplatin ; administration & dosage ; DNA-Binding Proteins ; genetics ; metabolism ; Drug Resistance, Neoplasm ; Endonucleases ; genetics ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasms, Glandular and Epithelial ; drug therapy ; metabolism ; surgery ; Ovarian Neoplasms ; drug therapy ; metabolism ; surgery ; Paclitaxel ; administration & dosage ; RNA, Messenger ; metabolism ; Repressor Proteins ; genetics ; metabolism ; Tubulin ; genetics ; metabolism

PURPOSE: Tumor marker concentrations in a given specimen measured by different analyzers vary according to assay methods, epitopes for antibodies used, and reagent specificities. Although great effort in quality assessment has been instituted, discrepancies among results from different analyzers are still present. We evaluated the assay performance of the UniCel(TM) DxI 800 automated analyzer in measuring the alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, CA 15-3 and CA 19-9 tumor markers. MATERIALS AND METHODS: The linearity and precision performance of the five tumor marker assays were evaluated, and concentrations of the respective markers as measured by DxI were compared to those measured by other conventional analyzers (ADVIA Centaur(TM) and Vitros(TM) ECi) using 200 specimens collected from 100 healthy persons and 100 patients with respective cancers. RESULTS: The linear fits for all five tumor markers were statistically acceptable (F=4648 for AFP, F=15846 for CEA, F=6445 for CA 125, F=2285 for CA 15-3, F=7459 for CA 19-9; p<0.0001 for all). The imprecision of each tumor marker assay was less than 5% coefficient of variation, except for low and high concentrations of AFP. The results from UniCel(TM) DxI 800 were highly correlated with those from other analyzers. CONCLUSION: Our results demonstrate that UniCel(TM) DxI 800 has good linearity and precision performance for the tumor markers assayed in this study. However, there were discrepancies between assaying methods. Efforts to standardize tumor marker assays should be undertaken, and the redetermination of cut-off levels is necessary when developing methods of analyzing tumor markers.
CA-125 Antigen/blood ; CA-19-9 Antigen/blood ; Carcinoembryonic Antigen/blood ; Humans ; Immunoassay/*instrumentation/*methods ; Tumor Markers, Biological/*blood ; alpha-Fetoproteins/metabolism

OBJECTIVETo investigate the clinical value of combination of human epididymis protein 4 (HE4), CA125 and the Risk of Ovarian Malignancy Algorithm (ROMA) in diagnosis of ovarian carcinoma.

METHODSTo detect the serum concentration of HE4 using ELISA and CA125 using ECL in patients of ovarian carcinoma group (n = 119), borderline ovarian tumor group (n = 36), benign ovarian neoplasm group (n = 96) and female healthy control group (n = 53). The ROMA based on the serum level of CA125, HE4 and a woman's menopausal status was used to calculate the predicted probability (PP) and diagnostic results of ovarian cancers.

RESULTSThe receiver operating characteristic (ROC) analysis showed the cut-off value was 67.3 pmol/L (the AUC was 0.906, the sensitivity was 80.7% and specificity was 94.6%). The serum levels of HE4 and CA125 in the ovarian carcinoma group were significantly higher than that in the borderline ovarian tumor group, benign ovarian neoplasm group and female healthy control group (P < 0.01). The serum levels of CA125 and HE4 showed statistically no significant difference between the borderline ovarian tumor group and benign ovarian neoplasm group (P > 0.05). The levels of HE4 and CA125 were reduced significantly in ovarian patients after surgery therapy (P < 0.01). The sensitivity and specificity of HE4 + CA125 combination was 92.7% and 72.5%. The ROMA that can classify patients into high and low risk groups was established as 9.3% in premenopausal and 27.3% in postmenopausal women.

CONCLUSIONSHE4 is a helpful biomarker for ovarian carcinoma diagnosis. Biomarker combination of HE4 and CA125, and applying of the ROMA are helpful to improve the accuracy in diagnosis of ovarian cancers.

Adenocarcinoma, Mucinous ; blood ; diagnosis ; surgery ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; blood ; CA-125 Antigen ; blood ; Cystadenocarcinoma, Serous ; blood ; diagnosis ; surgery ; Cystadenoma, Serous ; blood ; diagnosis ; surgery ; Endometriosis ; blood ; diagnosis ; Female ; Humans ; Menopause ; Middle Aged ; Ovarian Neoplasms ; blood ; diagnosis ; surgery ; Proteins ; metabolism ; ROC Curve ; Sensitivity and Specificity ; Teratoma ; blood ; diagnosis ; surgery ; Young Adult

OBJECTIVETo investigate the tumor-associated antigen CA125 expression in the serum and cervical and vaginal secretions in women during normal reproductive period, and explore the clinical value of detecting tumor markers in the cervical and vaginal secretions.

METHODSA total of 145 women in reproductive period were divided into 3 age groups (20-29 years, 30-39 years, and over 40 years), and their CA125 levels in cervical secretion, vaginal secretion and serum were detected by automatic electro-chemiluminescent immunoassay.

RESULTSCA125 levels in the cervical secretion, vaginal secretion and serum showed no significant difference between the 3 age groups (P>0.05). In each group, CA125 levels differed significantly between the cervical secretion, vaginal secretion and serum (P<0.001). In the 145 women, the average CA125 level was 497.82 - or + 75.29 U/ml in the cervical secretion, 114.66 - or + 26.40 U/ml in vaginal secretion and 18.06 - or + 3.35 U/ml in serum, showing significant differences between them (P<0.001).

CONCLUSIONCA125 expression level is significantly higher in the cervical and vaginal secretions than in the serum in women in normal reproductive period, and its levels in cervical and vaginal secretions can be more sensitive and convenient for early detection of related diseases.

Adult ; Biomarkers ; analysis ; CA-125 Antigen ; blood ; metabolism ; Cervix Mucus ; metabolism ; Female ; Humans ; Middle Aged ; Vagina ; secretion ; Young Adult