Maternal Urinary Carbohydrate Antigen 19-9 as a Novel Biomarker for Evaluating Fetal Hydronephrosis: A Pilot Study.

OBJECTIVE: To evaluate maternal urinary CA19-9 as a potential marker to diagnose severe antenatal hydronephrosis (ANH) during pregnancy and to compare the values with those in normal pregnancies as controls. PATIENTS AND METHODS: A total of 20 women in their third pregnancy trimester were enrolled. An anteroposterior pelvic diameter (APD) of ≥15 was considered as severe ANH. Case group consisted of 10 women with a diagnosis of severe ANH. Ten women with similar age, gestational age, fetal sex, normal ultrasonography, and no history of any congenital anomalies were chosen as controls. Urine samples were collected and maternal urinary CA19-9 was measured. The levels in case and control groups were compared using Mann-Whitney U test. RESULTS: Each group consisted of nine mothers with male fetuses and one with female fetus. The APD in the ANH group ranged from 17 to 40 mm. Five of 10 children in the ANH group also had contralateral APD of ≥4 mm (bilateral ANH). The mean age and gestational age of pregnant women in the two groups were comparable. The mean maternal CA19-9 was significantly higher in the ANH group compared with the controls (mean: 134.5 U/mL vs 22.2 U/mL, P < .001). CONCLUSION: To our best knowledge, this is the first time that maternal urinary CA19-9 has been used as a marker for ANH. Based on these pilot data, CA19-9 levels are significantly higher in the urine of pregnant women carrying fetuses with severe ANH, and it may have the potential to serve as a noninvasive and useful biomarker to diagnose ANH.

Identification of a Three-Biomarker Panel in Urine for Early Detection of Pancreatic Adenocarcinoma.

PURPOSE: Noninvasive biomarkers for early detection of pancreatic ductal adenocarcinoma (PDAC) are currently not available. Here, we aimed to identify a set of urine proteins able to distinguish patients with early-stage PDAC from healthy individuals. EXPERIMENTAL DESIGN: Proteomes of 18 urine samples from healthy controls, chronic pancreatitis, and patients with PDAC (six/group) were assayed using GeLC/MS/MS analysis. The selected biomarkers were subsequently validated with ELISA assays using multiple logistic regression applied to a training dataset in a multicenter cohort comprising 488 urine samples. RESULTS: LYVE-1, REG1A, and TFF1 were selected as candidate biomarkers. When comparing PDAC (n = 192) with healthy (n = 87) urine specimens, the resulting areas under the receiver-operating characteristic curves (AUC) of the panel were 0.89 [95% confidence interval (CI), 0.84-0.94] in the training (70% of the data) and 0.92 (95% CI, 0.86-0.98) in the validation (30% of the data) datasets. When comparing PDAC stage I-II (n = 71) with healthy urine specimens, the panel achieved AUCs of 0.90 (95% CI, 0.84-0.96) and 0.93 (95% CI, 0.84-1.00) in the training and validation datasets, respectively. In PDAC stage I-II and healthy samples with matching plasma CA19.9, the panel achieved a higher AUC of 0.97 (95% CI, 0.94-0.99) than CA19.9 (AUC = 0.88; 95% CI, 0.81-0.95, P = 0.005). Adding plasma CA19.9 to the panel increased the AUC from 0.97 (95% CI, 0.94-0.99) to 0.99 (95% CI, 0.97-1.00, P = 0.04), but did not improve the comparison of stage I-IIA PDAC (n = 17) with healthy urine. CONCLUSIONS: We have established a novel, three-protein biomarker panel that is able to detect patients with early-stage pancreatic cancer in urine specimens.

Bladder tumor markers: need, nature and application. 2. Tumor and tumor-associated antigens.

Despite the diversity of the available markers, none is truly specific to transitional epithelium, let alone its tumors. Some of the markers used, such as hCG and CEA, are far better known in other fields and seem to be expressed in only a minority of urothelial tumors. The majority of the available markers are tumor associated and should perhaps be considered as by-products of the process of malignancy in the urinary tract. Newer tests which are simple, rapid and easy to use have a practical advantage. These are currently the Bard BTA, BTA Stat and Aura-Tek FDP tests. So far, these markers have achieved only an arguable and marginal role in daily clinical practice, challenging the role of cytology and helping decide the type of cystoscopy. A more substantial role awaits a test with higher and more consistent sensitivity and specificity, together with the capability to provide independent diagnostic and/or prognostic information. In this part of the review we examine the literature view of the above-mentioned tests, as well as other new and some older tests such as blood group-related antigens, Lewis antigen, cytokeratins and others.

Purification and characterization of the MUC1 mucin-type glycoprotein, epitectin, from human urine: structures of the major oligosaccharide alditols.

The MUC1 glycoprotein, epitectin, a component of the human bladder epithelium, was purified from human urine. Sedimentation equilibrium analysis and gel filtration using polysaccharide or protein standards revealed a polydisperse preparation with molecular weights ranging from about 0.9 to 1.3 x 10(6). This suggests that in the native state epitectin exists as aggregates of three or four monomer units of 350-400 kDa. Epitectin was found to have significant affinity to hexyl-, octyl- or phenyl agarose indicating that hydrophobic interactions and possibly carbohydrate-carbohydrate interactions may be responsible for the self-association. Chemical and enzymic deglycosylation of [125I]-labeled urine epitectin and metabolically labeled H.Ep.2 epitectin resulted in extremely polydisperse products. The buoyant densities of epitectin purified from urine and H.Ep.2 cells were found to be 1.39-1.40 g ml(-1), suggesting that the total carbohydrate content of these preparations is not significantly different. The O-linked saccharides of epitectin were fractionated by HPLC and analyzed by permethylation and FAB-MS. The neutral saccharides from both sources contain three common structures, namely Gal1 --> 3GalNAc, GlcNAc1 --> 6 (Gal1 --> 3) GalNAc and Gal1 --> 4GlcNAc --> 6 (Gal1 --> 3)GalNAc. The sialic acid of urine epitectin consisted entirely of N-acetylneuraminic acid. The two sources of epitectin, in vitro labeled on sialic acid, were found to have the same sialyl oligosaccharides but in different proportions. Metabolic labeling and N-glycanase susceptibility experiments firmly established the presence of N-linked saccharides in epitectin as minor components. The remarkable similarities in the total carbohydrate content, the carbohydrate composition and structures of saccharides between epitectin from urine, a non-malignant source, and H.Ep.2 cells is surprising in view of the prevailing view that MUC1 glycoproteins of cancer cells are underglycosylated compared to those produced by non-malignant cells.

Toward salivary-urinary chronosensitivity testing: chronomes of OVX1, M-CSF and CA130.

Several rhythmic components were previously mapped for salivary and/or urinary CA125 and CA130. On the background of such reference standards, OVX1 and M-CSF were assayed on 242 urine samples and 160 saliva samples provided by a 71-year-old patient with a Müllerian/ovarian adenocarcinoma. Serum OVX1 correlates with serum CA125 (P = 0.002); when circulating CA125 concentrations decreased (from 122 to 14 U/ml), the urinary excretion rate of OVX1 decreased (P = 0.005), whereas the urinary excretion rate of CA125 increased (P < 0.001). Salivary OVX1 and urinary M-CSF show ultradian variations (with a frequency of one cycle in 14-17 hours), which could be utilized to guide treatment timing targeted first to optimize treatment efficacy and as a second consideration to minimize treatment toxicity.

Immunocytochemical determination of the tumor-associated glycoproteins MCA, CA 125 and BW 495/36-P in urine of patients with epithelial tumors of the kidney and urinary bladder.

Pre-operative and, in some cases, post-operative urine samples from 29 patients with renal cell or urinary bladder carcinoma were compared to samples from 24 healthy persons and 10 patients with nephrolithiasis and 9 patients with other benign disorders of the efferent urinary tract. The specimens were examined for the presence of MCA, CA 125 and BW 495/36-P expressing epithelial cells. The urine concentrations of the soluble antigens MCA and CA 125 were determined simultaneously in urine samples from 35 patients with renal cell or urinary bladder carcinoma, 10 patients with cystitis and 30 healthy individuals. MCA and BW 495/36-P expressing epithelial cells were significantly increased in all pre-operative urine samples of the tumor patients compared to the group of healthy persons. This increase was also seen with CA 125-positive cells in patients with bladder carcinoma, not however in patients with renal cell carcinoma. BW 495/36-P positive cells were also found in both groups of tumor patients in greater numbers than in the patients with nephrolithiasis or other benign urinary tract disorders. Based on a specificity of 97% when compared to the control urine samples, the cytological determination of the antigens MCA, CA 125 and BW 495/36-P in urinary tract cells of all tumor patients revealed a sensitivity of 48%, 33% and 79% as well as a positive predictive value of 92%, 89% and 95%, respectively. The sensitivity of CA 125 increased to 67% upon isolated analysis of patients with bladder carcinoma. The majority of labelled cells were not identifiable as tumor cells morphologically and appeared as normal transitional epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

[The values of urine cysteine protein activity in the diagnosis of ovarian cancer].

The levels of urine cysteine protease (UCP) were detected in the urines of 70 gynecological cancers, 50 gynecological benign tumors and 50 normal women. The values of UCP assay of gynecological cancers were much higher than those of benign and normal samples (P < 0.01). Best cut off point for diagnosis of gynecological cancers was P95 and UCP cut off value was 0.24 pmol.min-1/L by using percentile and ROC curve. The sensitivity of UCP assay was 90%, specificity 80% and accuracy 86%. The sensitivity for ovarian cancers was 95%, but 77% and 85% for corpus and cervical cancers respectively. There were no differences between UCP and CA125 (sensitivity 85%, specificity 87%, accuracy 84%) in the diagnosis of ovarian cancers. In 7 cases of 8 cases of stage I ovarian cancers, UCP were abnormal. In 6 cases of the same group, CA125 were normal (< 35,000 U/L). So UCP may be better than CA125 in the diagnosis of early ovarian cancer. The sensitivity of lactate dehydrogenase (LDH) isoenzyme was 75% in ovarian cancer which was lower than UCP and CA125, but the specificity 85%. LDH isoenzyme still was one of important tumor markers for diagnosis. Combined assays with UCP, CA125 and LDH isoenzyme may reach the sensitivity 96% and specificity 100% evidently. These data implied that UCP may be a good tumor marker in gynecological cancers especially for ovarian cancers in future.

Urinary levels of tumour associated antigens (CA 19-9, TPA and CEA) in patients with neoplastic and non-neoplastic urothelial abnormalities.

The urinary excretion of carbohydrate antigen 19-9 (CA 19-9), tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA) was evaluated in 264 patients with bladder cancer. Cut-off levels were established using a pool of healthy blood donors. The combined determination of CA 19-9 and TPA had a sensitivity of 74% in pTa and 83% in pT1 tumours, and 62% in grade 1, well differentiated tumours. Absence of disease at follow-up was related to a significant decrease in CA 19-9 and TPA in 129 patients with superficial (pTa or pT1) bladder carcinoma, followed up for at least 3 years. Recurrences, defined as new tumours at the same site or elsewhere in the bladder, were associated with an increase in the mean values but this was not statistically significant. A poor prognosis was indicated in patients with infiltrating tumours and the following pre-operative levels: TPA > 1500 u/l or CA 19-9 > 300 u/ml or CEA > 50 ng/ml.

Ontogeny of CA 125 antigen in pregnancy: immunoradiometric determination in amniotic fluid and immunohistochemical localization in fetal membranes.

CA 125 antigen was measured in amniotic fluid, maternal blood, cord blood, and fetal urine by a commercially available immunoradiometric assay kit. The amniotic fluid was obtained from 99 normal pregnancies at various gestational ages. The mean antigen levels were 29,676, 3350, and 1680 U/ml in amniotic fluid of the first, second, and third trimesters, respectively. In maternal blood, 12.5% of pregnant women in the first trimester of pregnancy showed elevated levels of CA 125 (65 to 100 U/ml). Late in gestation, CA 125 levels in cord blood and fetal urine were always less than 65 U/ml. Immunohistochemical study of CA 125 in fetal membranes, placenta, and decidua showed the presence of antigen only in the amnion. These results suggest that CA 125 is shed into amniotic fluid directly from the amniotic membrane.