CA125 Concentrations Research Articles

Evaluation of selected angiogenic and inflammatory markers in endometriosis before and after danazol treatment

Angiogenesis and inflammation are pivotal processes in developing endometriosis in the peritoneal cavity. The aim of the present study was to evaluate these two processes in women with endometriosis who had been treated with danazol to determine the sensitivity of a non-invasive test in diagnosing endometriosis. The clinical follow-up study was conducted in a group of 103 women diagnosed laparoscopically with endometriosis. Thirty-five patients qualified for danazol treatment. Pain was assessed using a visual analogue scale, whereas endometriosis was assessed using the revised American Society of Reproductive Medicine (rASRM) scale. Cancer antigen (CA)-125 and C-reactive protein (CRP) concentrations in plasma and peritoneal fluid were determined by immunoenzymatic methods, whereas vascular endothelial growth factor (VEGF) and interleukin (IL)-1β concentrations in plasma and peritoneal fluid were determined by ELISA. Endometrial expression of IL-8 and platelet-derived growth factor alpha polypeptide (PDGF-A) was determined using real-time polymerase chain reaction (PCR). Women with endometriosis (68.9% of patients) had higher plasma concentrations of CA-125, as well as higher concentrations of both CA-125 and VEGF in the peritoneal fluid. Endometrial expression of IL-8 mRNA was significantly higher, whereas that of PDGF-A was significantly lower, in contrast. After danazol treatment the patients reported lower pain scores; in addition, CA-125 concentrations in the plasma were decreased (P<0.001), whereas VEGF concentration in the plasma increased (P=0.009). For the diagnosis of endometriosis, none of the combinations of given markers had a sensitivity >60%. Danazol treatment is highly effective in relieving pain and decreasing CA-125 concentrations in the plasma. Higher plasma concentrations of VEGF after treatment could imply stimulation of angiogenesis.

Analysis of prognostic factors after radical resection in 628 patients with stage II or III colon cancer

To analyze the clinicopathologic factors related to recurrence and metastasis of stage II or III colon cancer after radical resection. The clinical and pathological data of 628 patients with stage II or III colon cancer after radical resection from Jan. 2005 to Dec. 2008 in our hospital were retrospectively reviewed and analyzed. The overall recurrence and metastasis rate was 28.5% (179/628). The 5-year disease-free survival (DFS) rate was 70.3% and 5-year overall survival (OS) rate was 78.5%. Univariate analysis showed that age, smoking intensity, depth of tumor invasion, lymph node metastasis, TNM stage, gross classification, histological differentiation, blood vessel tumor embolus, tumor gross pathology, multiple primary tumors, preoperative and postoperative serum concentration of CEA and CA19-9, and the regimen of adjuvant chemotherapy were correlated to recurrence and metastasis of colon cancer after radical resection. Multivariate analysis showed that regional lymph node metastasis, TNM stage, the regimen of postoperative adjuvant chemotherapy, and preoperative serum concentration of CEA and CA19-9 were independent factors affecting the prognosis of colon cancer patients. Regional lymph node metastasis, TNM stage, elevated preoperative serum concentration of CEA and CA19-9, the regimen of postoperative adjuvant chemotherapy with single fluorouracil type drug are independent risk factors of recurrence and metastasis in patients with stage II-III colon cancer after radical resection.

Does CA125 binding to mesothelin impact the detection of malignant mesothelioma?

The biomarker mesothelin is a useful diagnostic tool in malignant mesothelioma (MM) patients. It has high specificity but a sensitivity of only 50%. As mesothelin binds CA125, and as CA125 is often elevated in MM, we asked whether this binding affected measurable mesothelin levels in a relevant clinical setting. Mesothelin and CA125 concentrations were measured in the serum of 41 patients with MM. An assay was developed to detect mesothelin bound to CA125. Mesothelin was demonstrated to be bound by CA125 in 9 of 41 MM patients. This binding could be broken by the addition of sodium dodecyl sulphate and diethylenetriaminepenta acetic acid (DTPA) to the samples, however this did not lead to any change in the mesothelin level measured. We therefore conclude that binding of mesothelin to CA125 does not alter the measurement of mesothelin for the detection of MM.

Significance of HE4 estimation in comparison with CA125 in diagnosis of ovarian cancer and assessment of treatment response

BackgroundHuman epididymis protein 4 (HE4) is a novel and specific biomarker for ovarian cancer. The aim of this study is to evaluate a new tumor marker, HE4, in comparison with CA125 in diagnosis of epithelial ovarian cancer (EOC) and benign gynecological diseases.MethodsCA125 and HE4 serum levels were determined in 30 patients with epithelial ovarian cancer (21 serous, 6 endometrioid and 3 mucinous tumors), 20 patients with benign gynecological diseases (8 patients with ovarian cyst, 5 patients with endometriosis, 4 patients with fibroid and 3 patients with pelvic inflammatory disease) and 20 healthy women. CA125 and HE4 cut-offs were 35 U/ml and 150 pmol/l, respectively.ResultsSerum HE4 and CA125 concentrations were significantly higher in the ovarian cancer patients compared with those seen in patients with benign disease or in the healthy controls (p = 0.001 and p < 0.001 respectively). In the receiver operating characteristic analysis (ROC), the area under the curve (AUC) values for HE4 was 0.96 (95% confidence interval, 0.9-1.0) and CA125 was 0.82 (95% confidence interval, 0.7-0.94). Compared to CA125, HE4 had higher sensitivity (90% vs. 83.3%), specificity (95% vs. 85%), PPV (93.1% vs. 80.7%) and NPV (92.7% vs. 87.2%), the combination of HE4 + CA125 the sensitivity and PPV reached 96.7% and 97% respectively.ConclusionMeasuring serum HE4 concentrations along with CA125 concentrations may provide higher accuracy for detecting epithelial ovarian cancer.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1060413168685759

Huge uterine leiomyoma with degenerative changes mimicking ovarian carcinoma – a case report

Leiomyomas are the most common benign uterine tumors. Although 20-40% of all women in reproductive age may have uterine leiomyomas, they are not very common in pregnancy. Only 0.3-2.6% af all pregnant women are diagnosed with leiomyomas. The leiomyomas are symptomatic in 20-50% of all cases. Clinical symptoms are usually excessive or irregular menstrual bleeding, problems resulting from adjacent organs pressure, sterility miscarriage or problems during the labour. Leiomyomas are known to have estrogen receptors and can demonstrate an extensive growth in high estrogens concentration environment. During the pregnancy they can grow, stay the same size or as well decrease. Rapid leiomyoma's growth, caused by its transformation into sarcoma, takes place in about 0.1-0.8% of all cases. In this article we present a case of patient with leiomyoma, which rapid growth, which imitated ovarian tumor. A 40-year old patient was admitted to the 1st Department of Obstretrics and Gynecology Medical University of Warsaw, in May 2012 because of a large abdominal tumor. She had four vaginal deliveries and one cesarean section. The patients delivered three months before admission. Since the labour she had suffered from dysuria and noticed a quick waits enlargement. On admission the patient was in good general condition, without any stomachache. A giant tumor in her lower and middle abdomen was found. The tumor reached three fingers above the navel. In the ultrasound scan a large solid-cystic the tumor with moderate vascularization was described. It looked like the ovarian neoplasm. The CA-125 plasma concentration was 389,5 IU/ml. After giving a written informed consent the patient had an operation. During the operation a solid-cystic peducled uterine tumor was diagnosed. The diameter of the tumor was about 25 cm. The uterine and uterine appendages had no pathological macroscopic changes. Intraoperative histopathological examination was carried out and revealed mesenchymal tumor without evident polymorphism or mitosis. Because of lack of any signs of malignancy during the operation only the tumor with its peduncle was removed. The patient was discharged in good general condition after three day of postoperative hospitalization. The final histopathological examination revealed leiomyoma with cystic degeneration changes. A small focus of necrosis and extravasation was found. 4 weeks after the operation there were no abnormalities in the gynecological examination and the CA-125 concentration was 27 IU/ml. The presented case illustrates diagnostic difficulties, which may occur when atypical rapid tumor enlargement and its ultrasound image and laboratory tests results imitate ovarian tumor.

The plasma concentration of VEGF, HE4 and CA125 as a new biomarkers panel in different stages and sub-types of epithelial ovarian tumors

BackgroundVEGF may play a role in the pathogenesis of cancer disease, for example in cell growth, proliferation and angiogenesis. In this study, we investigated plasma levels of this cytokine in comparison to plasma levels of a new biomarker - HE4 and the established tumor marker CA125 in ovarian cancer patients (100) as compared to control groups: patients with a benign ovarian tumor (80) and healthy subjects (50).MethodsPlasma levels of VEGF were determined by ELISA, HE4 and CA125 by CMIA method.ResultsThe results showed that levels of VEGF, CA125 and HE4 were significantly higher in ovarian cancer (OC) patients as compared to the both control groups. VEGF has demonstrated as high as comparative markers values of the diagnostic sensitivity (SE), specificity (SP), the predictive values of positive and negative test results (PV-PR, PV-NR), and the area under the ROC curve (AUC) in early stages of cancer tested groups. The combined use of parameters studied resulted in the increase in the diagnostic criteria values and the AUC.ConclusionsThese findings suggest the usefulness of VEGF in the early diagnostics of ovarian cancer, especially in combination with CA125 and HE4, as a new biomarkers panel. Additionally, VEGF is the most useful tool in the diagnostics of locally advanced ovarian cancer without metastases. Investigated cytokine presented similar to HE4 usefulness in differentiation of OC according to its histopathlogical sub-type, and could be used especially in the diagnostics of endometrioid epithelial OC.

A Study of Amplifying Ovarian Cancer Biomarkers Concentration by an Ultrasonic Device

This paper reported a method of amplifying ovarian biomarkers concentration. Ultrasound device radiated to ovarian cancer cell to amplify the concentration of the biomarkers in the blood, achieving early diagnosis of ovarian cancer. The device used digital frequency generator technique and adaptive load technology to produce frequency(1MHz), duty cycle (50%), power(0.3W/cm2). This study used the device to produce ultrasound exposure on vitro ovariancancer cell and determined the concentration of CA125 and CA19-9 in the blood after ultrasound exposure. The results show that the device can produce stable frequency and ultrasound power. The device radiated vitro ovarian cancer cell 5min, the biomarker CA125 concentration amplified 2.02 fold and CA19-9 concentration amplified 4.21 fold compare with no radiation ovarian cancer cell. This project developed a device for amplifying ovarian cancer biomarkers concentration which can amplify two or more biomarkers concentration simultaneously.

An Immune AuRu Nanoalloy Probe for Trace CA125 Using Resonance Rayleigh Scattering as Detection Technique

The AuRu nanoalloy (GR) which Au/Ru molar ratio of 32:1 was prepared by the sodium borohydride reduction method. In the condition of pH 6.0, the GR was used to label CA125 antibody (Ab) to obtain an immunonanoprobe for CA125 (GRAb). In pH 7.0 citric acid-Na2HPO4 buffer solution, GRAb was aggregated nonspecifically to big clusters, which showed a strong resonance Rayleigh scattering (RRS) peak at 278nm. When CA125 was added, GRAb reacted specifically with CA125 and GR dispersive in the solution, which led to the RRS intensity decreased greatly. The decreased RRS intensity was linear to the concentration of CA125 in the range of 1.3-80 U/mL, a detection limit of 0.81 U/mL. The proposed method was applied to detect CA125, with satisfactory results.

Is CA72-4 a Useful Biomarker in Differential Diagnosis between Ovarian Endometrioma and Epithelial Ovarian Cancer?

Background. Surgical excision of ovarian endometriomas in patients desiring pregnancy has recently been criticized because of the risk of damage to healthy ovarian tissue and consequent reduction of ovarian reserve. A correct diagnosis in cases not scheduled for surgery is therefore mandatory in order to avoid unexpected ovarian cancer misdiagnosis. Endometriosis is often associated with high levels of CA125. This marker is therefore not useful for discriminating ovarian endometrioma from ovarian malignancy. The aim of this study was to establish if the serum marker CA72-4 could be helpful in the differential diagnosis between ovarian endometriosis and epithelial ovarian cancer. Methods. Serums CA125 and CA72-4 were measured in 72 patients with ovarian endometriomas and 55 patients with ovarian cancer. Results. High CA125 concentrations were observed in patients with ovarian endometriosis and in those with ovarian cancer. A marked difference in CA72-4 values was observed between women with ovarian cancer (71.0%) and patients with endometriosis (13.8%) (P < 0.0001). Conclusions. This study suggests that CA72-4 determination can be useful to confirm the benign nature of ovarian endometriomas in women with high CA125 levels.

Longitudinal Screening Algorithm That Incorporates Change Over Time in CA125 Levels Identifies Ovarian Cancer Earlier Than a Single-Threshold Rule

Longitudinal algorithms incorporate change over time in biomarker levels to individualize screening decision rules. Compared with a single-threshold (ST) rule, smaller deviations from baseline biomarker levels are required to signal disease. We demonstrated improvement in ovarian cancer early detection by using a longitudinal algorithm to monitor annual CA125 levels. We retrospectively evaluated serial preclinical serum CA125 values measured annually in 44 incident ovarian cancer cases identified from participants in the PLCO (Prostate Lung Colorectal and Ovarian) Cancer Screening Trial to determine how frequently and to what extent the parametric empirical Bayes (PEB) longitudinal screening algorithm identifies ovarian cancer earlier than an ST rule. The PEB algorithm detected ovarian cancer earlier than an ST rule in a substantial proportion of cases. At 99% specificity, which corresponded to the ST-rule CA125 cutoff ≥ 35 U/mL that was used in the PLCO trial, 20% of cases were identified earlier by using the PEB algorithm. Among these cases, the PEB signaled abnormal CA125 values, on average, 10 months earlier and at a CA125 concentration 42% lower (20 U/mL) than the ST-rule cutoff. The proportion of cases detected earlier by the PEB algorithm and the earliness of detection increased as the specificity of the screening rule was reduced. The PEB longitudinal algorithm identifies ovarian cancer earlier and at lower biomarker concentrations than an ST screening algorithm adjusted to the same specificity. Longitudinal biomarker assessment by using the PEB algorithm may have application for screening other solid tumors in which biomarkers are available.

Comparison of HE4, CA125 and ROMA algorithm in women with a pelvic mass: Correlation with pathological outcome

ObjectiveThe quality of first surgery is one of the most important prognostic factors in ovarian cancer patients. Pre-surgical distinction of benign and malignant pelvic mass plays a critical role in ovarian cancer management and survival. The aim of this study was to evaluate the clinical performance of ROMA algorithm and of CA125 and HE4 in the triage of patients with a pelvic mass undergoing surgery, in order to discriminate benign from malignant disease. MethodsThree hundred and forty-nine pre- and post-menopausal women, aged 18years or older undergoing surgery because of a pelvic mass were enrolled: serum concentrations of CA125 and HE4 were determined and ROMA was calculated for each sample. ResultsMedian serum CA125 and HE4 levels were higher in patients with EOC compared to subjects with benign disease (p<0.0001). The resultant accuracy (using Receiver Operating Characteristics, ROC Area) values for HE4, CA125 and ROMA showed a good performance ranging from 89.8% for CA125 in pre-menopausal patients to 93.3% for ROMA in post-menopausal patients: AUC for ROMA resulted significantly higher in comparison to CA125 alone (93.3% vs 90.3%, p=0.0018) in post menopausal patients. A sub-analysis considering the 40 patients with endometrioid disease showed the highest accuracy of HE4 in these patients. ConclusionsData presented confirm the accuracy of HE4 and of the ROMA algorithm in the distinction of ovarian carcinoma from benign disease, with a trend towards better performance for ROMA than for CA125 alone, statistically significant in postmenopausal patients.

Preoperative HE4 expression in plasma predicts surgical outcome in primary ovarian cancer patients: Results from the OVCAD study

ObjectivesEpithelial ovarian cancer (EOC) is the major cause of death due to gynecological malignancies. The most important prognostic factors are residual tumor mass after surgery and platinum-response. No predictive biomarkers are available to identify patients who will benefit from standard treatment. The aim of our study was to analyze the role of HE4 in predicting surgical and clinical outcome in primary EOC. MethodsIn the European multicentric project “OVCAD”, 275 consecutive patients with primary EOC were enrolled. Patients were eligible if radical cytoreductive surgery was performed and platinum-based chemotherapy was applied. Plasma and ascites samples were collected before or during surgery. The concentrations of HE4 and CA125 was determined using ELISA and Luminex technique, respectively. ResultsMedian age at first diagnosis was 58years (range 18–85years). Most patients presented with advanced stage disease, FIGO III or IV (94.6%), grades II–III (96%) and serous histology (86.2%). In most cases a complete cytoreduction to no residual tumor mass was achieved (68.4%). Higher plasma HE4 levels correlated with poor surgery outcome in terms of macroscopically residual tumor mass (p<0.001) and platinum-resistance (p=0.009). Plasma CA125 and the risk index (HE4 and CA125) were independent predictive factors for surgical outcome (p=0.001, OR=3.37, 95% CI=1.61–7.06 and p<0.001, OR=6,041, 95% CI=2.33–15.65, respectively). FIGO stage III was an independent predictive factor for platinum response (p=0.039, OR=0.436, 95% CI=0.198–0.960). ConclusionsThe presented data are showing that the combination of HE4 and CA125 expression in plasma might predict the surgical outcome in EOC and by this may have a prognostic impact on PFS and OS.

Huge Atypical Cyst Arising From the Pancreas

Question: A 68-year-old man who had no specific abdominal symptoms was found to have a huge pancreatic cyst on a screening computed tomography (CT) and was referred to our department for a diagnostic workup. On presentation, the patient seemed to be well-nourished and in good health. He was mildly diabetic, but had no history of alcohol abuse or pancreatitis. Abdominal CT showed a multicystic lesion measuring 8 cm located in the body of the pancreas. The lesion protruded craniad and was compressing the pancreatic parenchyma, main pancreatic duct, and surrounding anatomic structures including the common hepatic artery, the portal vein, the stomach, and the left lobe of the liver (Figure A). However, there was no evidence of invasion or regional lymph node swelling. CT revealed that the wall of the cyst was relatively thick and clearly enhanced, and the contents of the cysts were slightly denser than water. On magnetic resonance imaging, the contents of the cysts were slightly higher signal intensity than water on the T1-weighted images and slightly lower signal intensity in T2-weighted images (Figures B and C). Magnetic resonance cholangiopancreatography did not show any clear connection between the cysts and the pancreatic duct (Figure D). Abdominal ultrasonography showed a floating echo pattern within the cysts and a nodular structure suggesting an intracystic lesion was seen on the wall of the cyst (Figure E, arrow). The laboratory data showed a markedly elevated serum CA19-9 level (450 U/mL; reference range, <37) and s-pancreas-1 antigen (SPan-1) level (100.3 U/mL; reference range, <30). Other blood and blood chemistry data were unremarkable. What is the most likely diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Palpation of the lesion at laparotomy revealed an elastic hard mass with thick capsule that was mobile in relation to the surrounding structures (Figure F), and it could be enucleated with a very small portion of the pancreas from which the lesion seemed to have originated. Examination of the surgical specimen revealed a multicystic tumor filled with yellowish atheroma-like debris (Figure G). The concentrations of CA19-9 and SPan-1 in the cyst fluid were extremely high−34,123,900 U/mL and 353.6 U/mL, respectively. Microscopically, the inner surface of the cysts was lined by stratified squamous cells and well-developed lymphatic tissue was observed within the wall of the cysts (Figure H). The serum CA19-9 and SPan-1 levels had decreased dramatically to 54.4 and 25.1 U/mL, respectively, at 1 month after surgery. Lymphoepithelial cysts (LECs) are rare, non-neoplastic, benign pancreatic tumors first described in 1985.1Luchtrath H. Schriefers K.H. A pancreatic cyst with features of a so-called branchiogenic cyst.Pathologe. 1985; 6: 217-219PubMed Google Scholar Typically, LECs appear on CT as a multi- or unilocular, well-encapsulated, hypodense cystic lesion with an enhancing wall, and they often extend outside the pancreas.2Katz M.H.G. Mortenson M.M. Wang H. et al.Diagnosis and management of cystic neoplasms of the pancreas: an evidence-based approach.J Am Coll Surg. 2008; 207: 106-120Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar The clinical significance of tumor markers, such as CA19-9, in LECs has not been established. However, the findings in the present case suggested a clear association between the serum tumor markers and the tumor markers in the cyst. If a definitive diagnosis has been made, resection of LECs is not always necessary because of its benign nature. Endoscopic fine needle aspiration and cytology3Policarpio-Nicolas M.L. Shami V.M. Kahaleh M. et al.Fine needle aspiration cytology of pancreatic lymphoepithelial cysts.Cancer. 2006; 108: 501e6Crossref Scopus (39) Google Scholar may be an alternative means of selecting patients for invasive treatment. Surgical resection is considered only for symptomatic LECs or when malignancy cannot be ruled out because of the size of the tumor or the tumor marker levels. However, aggressive resection, including major pancreatectomy should be avoided when LEC is suspected preoperatively.

CA-125 concentration in serum and peritoneal fluid in patients with endometriosis - preliminary results.

IntroductionCancer antigen 125 (CA-125), known as a biomarker for women genital tract malignancies, could be also useful in detecting and monitoring endometriosis. The aim of this study was to evaluate CA-125 in serum and peritoneal fluid (PF) as an indicator of endometriosis.Material and methodsFifty-six patients admitted to the First Department of Obstetrics and Gynaecology for diagnostic or therapeutic laparoscopy conducted for infertility, pelvic pain, suspected endometriosis or ovarian cysts entered the study. Those with laparoscopically confirmed endometriosis were assigned to group A, those without this condition to group B. Blood for CA-125 was taken prior to surgery, centrifuged and assayed in accordance with the manufacturer's instructions (VIDAS CA-125 II). Peritoneal fluid and an endometrial biopsy were taken during laparoscopy. Statistical comparisons were performed using Statistica 7.1.ResultsGroup A consisted of 44 women with laparoscopically confirmed diagnosis; 15 patients served as a control group. The mean value of CA-125 concentration in the endometriosis group was 33.98 U/ml, vs. 9.3 U/ml in the control group. The mean value of CA-125 in peritoneal fluid was 1241.88 U/ml in the non-endometriosis group versus 2640.23 U/ml in the study group; both results were statistically significant (p < 0.05). There was a significant correlation between the stage of endometriosis and CA-125 plasma concentration (R = 0.5993, p < 0.001). Cancer antigen 125 concentration in serum was a moderate predictor to distinguish between patients with and without endometriosis (AUC 0.794; 95% CI 0.668-0.921; p = 0.001).ConclusionsCancer antigen 125 is a well-known biomarker for endometriosis and helpful in daily clinical practice when endometriosis is suspected. The cut-off value in serum suggesting endometriosis with 68% sensitivity is 11 U/ml. This value is normal range for Ca-125 concentration.

Preoperative CA-125 predicts extra-uterine disease and survival in uterine papillary serous carcinoma patients

We determined the clinical utility of preoperative serum CA-125 as predictor of extra-uterine disease and as prognosticator for survival in patients with uterine papillary serous carcinoma (UPSC). Patients diagnosed with UPSC, identified between 1992 and 2009, and with preoperative CA-125 measurement were included. A receiver operator characteristic (ROC) curve was used to quantify marker performance. Overall and progression free survival were analyzed using the Kaplan-Meier method. Regression analyses were used to investigate the association of preoperative CA-125 levels and other clinicopathological variables with the presence of extra-uterine disease and the effects on survival. Sixty-six patients met the study criteria. Using ROC, the CA-125 concentration of 45 U/mL as cutoff level provided the best sensitivity (75%) and specificity (74%) for extra-uterine disease, with a positive predictive value of 86%. Survival was significantly longer in patients with preoperative CA-125 ≤ 45 U/mL (p<0.001). Only preoperative CA-125 >45 U/mL remained significantly associated with extra-uterine disease (OR=6.30, 95% CI 1.93-20.62). Furthermore, advanced FIGO stage (HR=4.53, 95% CI 1.50-13.62) and preoperative CA-125 >45 U/mL (HR=3.12, 95% CI 1.13-8.73) were associated with decreased survival. Preoperative elevated serum CA-125 is an independent predictor for the presence of extra-uterine disease and an independent risk factor for survival in UPSC patients.

HE4 protein and SMRP: Potential novel biomarkers in ovarian cancer detection.

Epithelial ovarian cancer has the highest mortality of all gynecological cancers, and its progression is often without symptoms. Clinical outcome and survival may be improved if the disease is identified in the early stages. The objective of the study was to evaluate the utility of the serum biomarkers human epididymis protein 4 (HE4), soluble mesothelin-related protein (SMRP) and CA125 in the detection of ovarian cancer. In this retrospective study, the serum concentrations of CA125, HE4 protein and SMRP were measured in a cohort of 70 patients with epithelial ovarian cancer (EOC) compared with 78 healthy controls. Median serum levels of CA125 for ovarian cancer cases were 503.55±560.7 U/ml vs. 9.28±14.47 U/ml in the control group (p<0.001); for SMRP 5.13±7.64 nM vs. 1.02±0.89 nM (p<0.01); and for HE4 597.95±934.59 pM vs. 56.75±43.79 pM (p<0.001), respectively. Positive correlations between the clinical stage of EOC and CA125, HE4 and SMRP serum concentrations were found [(R=0.83; p<0.001); (R=0.64; p<0.001); (R=0.45; p<0.001), respectively]. Data analysis for the whole study group also revealed a significant correlation between plasma concentrations of CA125 and HE4 (R=0.45; p<0.001), between CA125 and SMRP (R=0.38; p<0.001) as well as HE4 and SMRP (R=0.51; p<0.001). Similar significant correlations between serum biomarker concentrations were also found in the ovarian cancer group [CA125 and HE4 (R=0.31; p<0.01); CA125 and SMRP (R=0.25; p<0.05); HE4 and SMRP (R=0.44, p<0.001), respectively]. A significant correlation was observed between the serous histological type of EOC and serum concentration of HE4 in the study group compared with other non-serous types of ovarian cancer (p<0.01). In conclusion, measuring CA125 in combination with new biomarkers such as SMRP and HE4 may improve the accuracy of ovarian cancer diagnosis, particularly in early detection of the disease.

PWE-133 Increased levels of neutrophil gelatinase associated lipocalin (NGAL) in the plasma of cholangiocarcinoma patients

IntroductionWe have previously demonstrated that the level of neutrophil gelatinase-associated lipocalin (NGAL) is increased in the bile of patients with pancreatobiliary malignancy. NGAL is expressed by activated neutrophils and many...

Human epididymis protein 4 as a serum marker for diagnosis of endometrial carcinoma and prediction of clinical outcome

The purpose of this study was to assess the diagnostic and prognostic impact of preoperative serum determination of human epididymis protein 4 (sHE4), and to investigate its potential correlation with clinicopathological features and survival endpoints in endometrial cancer patients. Preoperative serum samples from 193 endometrial cancer patients and 125 women with normal endometrium were measured for sHE4 and serum CA125 (sCA125) concentrations by quantitative chemiluminescent microparticle immunoassays on the automated Architect instrument. sHE4 concentrations were significantly higher in endometrial cancer patients regardless of tumour stage and grade compared with normal controls. Setting the specificity at 95 % , the sensitivities in detecting endometrial cancer patients were 66 % for HE4, 33 % for CA125 and 64 % for the combination of the two markers. High concentrations of both HE4 and CA125 significantly correlated with all clinicopathological features characterising a more aggressive tumour phenotype.In multivariate analysis, only high preoperative sHE4 concentrations, but not sCA125, were independent prognostic factors for shorter Overall Survival, Disease-Free Survival and Progression-Free Survival. HE4 is more sensitive and specifi c than CA125in distinguishing endometrial cancer patients from women with normal endometrium, regardless of tumour stage and grade. sHE4 appears to be associated with a more aggressive tumour variant and it could be clinically useful, in identifying high-risk endometrial cancer patients, for a tailored surgical and postoperative therapy. HE4 significant correlation with decreased Overall Survival, Disease Free Survival and Progression Free Survival suggests its potential role as a novel prognostic marker for endometrial cancer.

318 INCREASED LEVELS OF NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN (NGAL) IN THE PLASMA OF CHOLANGIOCARCINOMA PATIENTS

Introduction We have previously demonstrated that the level of neutrophil gelatinase-associated lipocalin (NGAL) is increased in the bile of patients with pancreatobiliary malignancy. NGAL is expressed by activated neutrophils and many other cell types and is thought to have bacteriostatic, pro-proliferative and pro-metastatic functions. NGAL can be detected in the blood plasma. We hypothesised that the plasma NGAL level is elevated in patients with cholangiocarcinoma (CC) compared with patients with primary sclerosing cholangitis (PSC), and with healthy volunteers. Methods Plasma samples were collected from 97 patients with confirmed CC, 62 patients with PSC and no CC and 82 healthy controls. Plasma NGAL quantification was performed in duplicate on plasma from each subject using a Quantikine ELISA kit (R&D Systems, Minneapolis, Minnesota, USA). CC and healthy control cohorts were compared using the Student t test and receiver operator characteristic (ROC) analysis. Differences between CC and PSC cohorts were then sought. Pearson9s correlation analysis was used to assess relationships between the levels of NGAL and other plasma markers. Results Median NGAL concentrations (range) in CC, PSC and healthy controls were 92 ng/ml (14–644), 83 (43–171) and 64 (29–132) respectively. NGAL levels were significantly higher in plasma from CC patients compared with healthy controls (p 2 =0.14), white cell count (r 2 =0.09), bilirubin (r 2 =0.01), ALP (r 2 =0.02) or creatinine (r 2 =0.03). There was moderate correlation between NGAL and Ca19-9 concentrations (r 2 =0.38). Conclusion NGAL is expressed at significantly higher concentrations in the plasma of patients with CC compared to plasma from healthy controls and from subjects with PSC. This finding appears to be independent of renal impairment, cholestasis or systemic inflammatory response, suggesting that NGAL may represent a novel plasma biomarker of CC. Competing interests None declared.

The Values of CA-125, Progesterone, ß-HCG and Estradiol in the Early Prediction of Ectopic Pregnancy

To explore the diagnostic value and measurement of serum CA-125, the single measurement of progesterone (P), ß-HCG, and estradiol (E2) in the early diagnosis of ectopic pregnancy. Serum levels of CA-125, progesterone, ß-HCG and estradiol were measured by Enzyme Linked Immuno Sorbent Assay (ELISA) techniques in 40 symptomatic women with ectopic pregnancy and 24 women with normal intrauterine pregnancy during gestational age of 4-10 weeks at Al-Kadhmiya Teaching Hospital, Baghdad, Iraq, between November 2010 and June 2011. The mean ±SEM serum levels of CA-125, progesterone, ß-HCG, and estradiol in patients with ectopic pregnancies (16.51±2.39U/ml; 2.54±0.47ng/ml; 72.75±12.27mIU/ml; 13.4±2.14pg/ml; respectively) were significantly lower than the levels in normal intrauterine pregnancies (74.25±18.5U/ml; 28.36±3.7ng/ml; 249.54±18.0mIU/ml; 112.7±23.6pg/ml; respectively). When using a CA-125 concentration of 20.5 U/ml as a cut-off value for the diagnosis of ectopic pregnancy, sensitivity was 75.7%, specificity 100%, the positive predictive value was 100% and the negative predictive value 71.4%. The measurement of CA-125 and progesterone levels is useful in discriminating ectopic from normal gestations.