Specificity and affinity of 26 monoclonal antibodies against the CA 125 antigen: first report from the ISOBM TD-1 workshop. International Society for Oncodevelopmental Biology and Medicine

The specificity of 26 monoclonal antibodies against the CA 125 antigen was investigated in two phases of the ISOBM TD-1 workshop. The binding specificity was studied using CA 125 immunoextracted by specific antibodies immobilized on various solid phases, or on the surface of human cell lines. Immunometric assays using all possible antibody combinations were used to study the topography of antibody binding sites on the antigen. We conclude that the CA 125 antigen carries only two major antigenic domains, which classifies the antibodies as OC125-like (group A) or M11-like (group B). One antibody, OV 197, showed binding specificity related to some of the OC125-like antibodies, but was classified into a separate group C. The OC125-like group of antibodies has four subgroups with different binding specificities. These are A1 = OC 125 and K 95, A2 = K 93, A3 = B43.13, and A4 = ZS 33, B27.1 and CCD 247. Binding of nonlabelled OC 125 or K 95 to CA 125 caused a marked increase in binding of labelled OV 197 to the complex. This conformational change was not observed with any other antibody combinations. Antibody B43.13 could form immunometric assay combinations particularly with antibodies of subgroup A4, indicating that the B43.13 epitope is in the periphery of the binding area of OC125-like antibodies. The M11-like group of antibodies is more homogenous with strong cross-inhibition between most antibodies. Only one antibody, ZR 38, would form an immunoassay combination with other M11-like antibodies and thus represents a distinct subgroup. The main group of M11-like antibodies are M 11, ZR 45, MA602-6, K 91, OV 185, K 101, K 90, K 96, K 97, K 102, CCD 242, 145-9, and 130-22. Antibody OV 197 binds to a domain designated C and is unique, as stated above. Antibody pairs from any two of the three groups may be used in immunometric assays. Three antibodies were not studied by complete cross-inhibition due to low affinity (OV 198 and K 100) or lack of material (MA602-1). OV 198 and K 100 are most likely OC125-like and MA602-1 is M11-like. Antibody affinity was estimated with labelled antigen in solution or with antigen absorbed on microtiter wells. Western blot analysis showed staining both in the stacking gel and corresponding to a molecule of 200 kDa. There was a marked difference between the antibodies in their ability to bind to CA 125 immobilized on a membrane. Strongest binding was observed with the M11-like antibodies, particularly M 11, K 96, K 97, MA602-6, 145-9. Antibodies belonging to the subgroup A4 were the only OC 125-like antibodies which reacted well with CA 125 in Western analysis. Digestion of CA 125 with proteolytic enzymes showed it to be particularly sensitive to trypsin cleavage. However, no low molecular weight fragments with preserved immunoreactivity were found.     

Purification and characterization of the CA 125 tumor-associated antigen from human ascites

CA 125 is an antigenic determinant associated with epithelial ovarian carcinomas, which is recognized by a monoclonal antibody, OC 125. The biochemical structure, the immunological characteristics and the physiological function of CA 125 are unknown, principally because the molecule expressing it has not been purified to homogeneity. In the present study, we developed a single, one-step method for purifying CA 125 by column affinity chromatography, using the OC 125 antibody as immobilized ligand. The column proved to be highly specific for the purification of CA 125 from human ascites (HA). The antigen that eluted from the column has a specific activity of 6,240 +/- 120 U of CA 125/mg protein, the specific activity in the initial HA samples being 100 +/- 12 U/mg protein. The purified, immunoreactive CA 125 (IR-CA 125) was shown to be proteinaceous in nature. SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and gel filtration characterization showed that the purified antigen exists as a high molecular weight (MW) complex, of up to 1.5 million daltons, which could be dissociated under strong denaturing conditions, giving rise to moieties with an apparent MW of 205 and 55 kD. IR-CA 125 was also associated with a lower MW protein, with an apparent MW of 10-15 kD. The 205-kD MW protein was immunoreactive CA 125, as measured by immunoradiometric assay after being electroeluted from the polyacrylamide gel. Furthermore, when the affinity-purified antigen was subjected to SDS-PAGE, followed by immunoblotting, the lane which was reactive with the iodinated OC 125 antibody gave rise to a band with a molecular mass of 205 kD. Our results suggest that, on an analytical scale, the affinity column is useful for the purification of CA 125. The purified antigen is being used to investigate the possible role of CA 125 in the growth, development and physiological characteristics of human ovarian carcinomas in in vitro studies.     

Tumor markers CA 125 and CA 19-9 in cord blood and during infancy: developmental changes and use in pediatric germ cell tumors

Tumor markers CA 125 and CA 19-9 are elevated in a variety of malignancies in adult patients, but only little is known of their biology during gestation or infancy. We have addressed the developmental pattern of these carbohydrate antigens in pediatric patients by measuring their serum levels in 133 cord blood samples from the second through third trimester of gestation and in 39 infants aged less than 1.5 y. The serum concentrations of both markers revealed developmental changes, the levels being higher at earlier gestation (wk 24 through 37) than at term or during infancy. The clinical value of the markers was evaluated by monitoring 26 children with germ cell tumors; 14 benign and 2 immature teratomas, and 11 malignant germ cell tumors. Patients with immature sacrococcygeal teratomas showed constant and prolonged elevations of serum CA 125 and CA 19-9. In contrast, all but two children with mature teratomas had normal marker levels; these two patients with abnormally high serum CA 125 and CA 19-9 values for the first 4 postoperative weeks had a benign ovarian and ventricular teratoma, respectively. Of the 11 children with malignant germ cell tumors, serum CA 125 or CA 19-9 concentration was elevated in four patients at diagnosis and declined to normal within 2 wk after institution of therapy. Malignant recurrence in two patients was not associated with a reelevation of the CA 125 level. Taken together, our results demonstrate a developmentally regulated pattern of serum CA 125 and CA 19-9. The carbohydrate markers were usually inferior to alpha-fetoprotein in monitoring of germ cell tumors, but may be a useful adjunct in the follow-up of immature teratomas.     

My association with Ludwik Hirszfeld, Wroc?aw 1945-1954

Intravenous injection of the murine monoclonal anti-CA125 antibody B43.13 (Ovarex: Ab1) into ovarian cancer patients led to the induction of an idiotypic network. Of the 75 patients who received one to ten injections of a 2-mg dose of the antibody, 48 developed anti-(mAb B43.13) antibodies (Ab2); 18 of these patients also had elevated levels of anti-[anti-(mAb B43.13)] antibodies (Ab3; = anti-CA125 antibodies) compared to pre-injection values. Characterization of these antibodies revealed that the binding to CA125 could be inhibited by mAb B43.13 in most samples. Human anti-CA125 antibodies or Ab3 purified from patient serum samples specifically recognized human ovarian tumor cells and tissues expressing CA125. In addition, these anti-CA125 antibodies were able to conduct Fc-mediated tumor cell killing (antibody-dependent cell-mediated cytotoxicity). This raises the possibility of using an Ab1 for anti-idiotype induction immunotherapy of cancer.     

OVCA (CA125) second generation: technical aspects and serum levels in controls, patients with liver disease, pregnant women and patients with ovarian disease

An immunoradiometric method of the second generation (IR-MA II) is widely used to determine CA125 serum levels. In this study we have evaluated the performance characteristics of a commercially available IRMA CA125 II (Byk-Gulden, Sangtec Diagnostica). The CA125 serum levels were determined in several groups of patients (healthy women, pregnant women, subjects affected by benign and malignant ovarian cancer, patients with liver diseases) with two IRMAs CA125 II (Byk-Gulden, Sangtec Diagnostica and Centocor, Diagnostic Division) and IRMA CA125 I (Byk-Gulden, Sangtec Diagnostica). Our results show a good analytic performance of IRMA CA125 II (Byk-Gulden, Sangtec Diagnostica), a good correlation between IRMAs CA125 II (Byk-Gulden, Sangtec Diagnostica and Centocor, Diagnostic Division), but an unacceptable correlation between IRMAs CA125 II (Byk-Gulden, Sangtec Diagnostica and Centocor, Diagnostic Division) and IRMA CA125 I. A statistically significant difference was observed comparing the values obtained with both IRMAs CA125 II and IRMA CA125 I in the groups of patients. In contrast no statistically significant difference was observed when we compared the values obtained with IRMA CA125 II (Byk-Gulden, Sangtec Diagnostica) and IRMA CA125 II (Centocor, Diagnostic Division). CA125 serum values obtained with the second-generation kits were different from those obtained with the first-generation one; consequently, it is important, especially in the follow-up of cancer patients, that CA125 serum values be obtained with kits of the same generation. Our data seem to suggest the use of second-generation kits to determine CA125 serum levels.     

Iodine-125-digoxin radioimmunoassay: comparison of commercial kits

Iodine-125-digoxin radioimmunoassay kits available from Abbott Diagnostics (AD), Dade Division (D), Schwarz/Mann (SM), and Clinical Assays (CA) were evaluated with respect to assay quality. The kit accuracies did not differ significantly at 2.0 ng/ml and the interassay coefficients of variation ranged from 9% (AD) to 21.4% (CA) The accuracy for all kits above 4 ng/ml is questionable, and since serum-dilution values correlated well with undiluted serum values, the dilution method of dose quantitation is preferable for levels above 4 ng/ml. Although all the kits were adequate, for evaluating digoxin at the 2ng/ml level, the Abott kit seems to be of slightly better quality.     

Biodistribution of charged F(ab')2 photoimmunoconjugates in a xenograft model of ovarian cancer

The effect of charge modification of photoimmunoconjugates (PICs) on their biodistribution in a xenograft model of ovarian cancer was investigated. Chlorin(e6)c(e6) was attached site specifically to the F(ab')2 fragment of the murine monoclonal antibody OC125, directed against human ovarian cancer cells, via poly-1-lysine linkers carrying cationic or anionic charges. Preservation of immunoreactivity was checked by enzyme-linked immunosorbent assay (ELISA). PICs were radiolabelled with 125I and compared with non-specific rabbit IgG PICs after intraperitoneal (i.p.) injection into nude mice. Samples were taken from normal organs and tumour at 3 h and 24 h. Tumour to normal 125I ratios showed that the cationic OC125F(ab')2 PIC had the highest tumour selectivity. Ratios for c(e6) were uniformly higher than for 125I, indicating that c(e6) became separated from 125I. OC125F(ab')2 gave highest tissue values of 125I, followed by cationic OC125F(ab')2 PIC; other species were much lower. The amounts of c(e6) delivered per gram of tumour were much higher for cationic OC125F(ab')2 PIC than for other species. The results indicate that cationic charge stimulates the endocytosis and lysosomal degradation of the OC125F(ab')2-pl-c(e6) that has bound to the i.p. tumour. Positively charged PICs may have applications in the i.p. photoimmunotherapy of minimal residual ovarian cancer.     

Serum CA125 measurement is useful in 3 cases with pericardial effusion

Previously we reported that serum CA125 level is elevated in cases of pericardial effusion. We report three cases in which serum CA125 measurement is useful for assessing clinical status. In case 1, a 19-year-old came to our hospital for cardiac tamponade. Moderate degree of pericardial effusion and high CA125 level were observed. After the pericardectomy the serum CA125 level was normalized and pericardial effusion disappeared. Case 2, a 50-year-old man with mesothelioma and in whom serum CA125 level was elevated with pericardial effusion. After cardiac drainage his condition improved, with decreased CA125 level. However, later the CA125 level rose and recurrent localized pericardial effusion with worsening condition was observed. In case 3, in a 78-year-old woman with pericardial effusion no recurrence was observed after pericardial drainage. Her CA125 value was normal. These results indicated that measurement of CA125 value is a useful marker for assessing the clinical course of this disease.     

The value of serum CA125 assays in the diagnosis of uterine adenomyosis

OBJECTIVE: To investigate the value of serum CA125 assays in the diagnosis of uterine adenomyosis. METHODS: Fifty-five consecutive patients with uterine-adenomyosis and twenty with leiomyoma of uterus, diagnosed by surgery and pathology were studied. The blood samples were taken one day before operation. Twenty normal healthy women were served as controls. CA125 levels were determined by radioimmunoassay method. RESULTS: The median (M) CA125 levels (Ql-Qu) for patients with adenomyosis, leiomyoma and normal controls were 102.1 (56.3-182.1)kU/L, 34.6 (33.7-43.8)kU/L and 33.1 (32.7-33.8)kU/L respectively. The differences among the three groups were all significant (P < 0.01). The CA125 positive rates (CA125 > 50kU/L) for the above three groups were 80.0%, 10.0% and 5.0% respectively. Patients with adenomyosis had a higher CA125 positive rate than those with leiomyoma or normal controls (P < 0.001). For patients with adenomyosis the CA125 levels were positively correlated with uterine size (r = 0.33, P < 0.05). The adenomyosis patients treating with sex hormone preparations were found to have lower CA125 levels in comparison with non-users (P < 0.05). The mean CA125 level measured in sixteen patients decreased significantly one week postoperation. CONCLUSIONS: Serum CA125 assay is of great assistance to the diagnosis of uterine adenomyosis as well as to the differential diagnosis between adenomyosis and leiomyoma of uterus.     

A risk model for ovarian carcinoma patients using CA 125: time to normalization renders second-look laparotomy redundant

BACKGROUND: We evaluated the incorporation of CA 125 normalization times into a prognostic model based on pretreatment variables in patients with ovarian carcinoma to determine if they could render second-look laparotomy (SLL) redundant. METHODS: A total of 54 consecutive patients with ovarian carcinoma who underwent SLL between 1985 and 1990 were included in this analysis. At diagnosis, all of the patients had abnormal CA-125 serum levels, which fell to within the normal range during chemotherapy. Cox's model was used to select pretreatment variables relevant for prognosis. The influence of the time to normalization of CA 125 (< or = vs. > 1 months) and the capability of SLL results to modify prognostic prediction, were also evaluated. RESULTS: The size of the residual tumor at the beginning of therapy, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently predictive of survival. The time to normalization of CA 125 serum levels (analyzed either as -a continuous or as a two-category variable) also had an independent prognostic role when included in the model. When we examined the inclusion of both CA 125 parameter and SLL into the model together, we found that only CA 125 continued to have an independent prognostic relevance. On the basis of the two pretreatment parameters (PS and tumor size) and of this response parameter (time to normalization of CA 125 values) we selected six subgroups of patients having different outcomes (log rank test of equality over-strata < 0.001). Patients with good prognostic pretreatment variables, and those with intermediate prognosis at the beginning of therapy who showed a quick normalization of CA 125, had an 80% 5-year survival, compared with 16% 5-year survival in the remaining patients. (P < 0.0001). CONCLUSIONS: Our data suggest that the survival of patients with advanced ovarian carcinoma could be accurately predicted by considering some pretreatment variables and time to CA 125 normalization together, without performing SLL. Our risk model, however, needs to be validated by larger prospective trials, to draw any definitive conclusions about the abandonment of surgically defined response.     

Mutagenicity and amount of chloroform after chlorination of bank filtered lake water

A one-step immunoassay for simultaneous detection of serum IgG and IgM antibodies to Borrelia burgdorferi has been developed. The assay is based on C1q, which binds to immune complexes containing IgG and/or IgM antibodies. Micro-beads pre-coated with antibodies to human C1q are mixed with human serum samples and fluorochrome-labelled B. burgdorferi flagellum antigen. In the presence of serum IgG and/or IgM antibodies to B. burgdorferi, fluorochrome-labelled antigen/antibody complexes are formed. These are then bound by serum C1q and are subsequently captured on the anti-C1q-coated beads. The sample is analysed on a flow cytometer and the presence of fluorescent beads is, thus, indicative of a positive test result. In the present study the sensitivity and specificity of the assay are compared to those of the indirect IDEIA B. burgdorferi IgG and the mu-chain capture IDEIA B. burgdorferi IgM ELISAs for separate determination of IgG and IgM. Detection using a flow cytometer can be performed without separation of the beads from the reaction mixture, which means that in practice, the method is carried out as a one-step assay and it is, thus, very suitable for automation. Other advantages of this kind of assay includes an antibody/antigen reaction which occurs in solution and the potential of using the method for the detection of antibodies against several antigens from the same or different infectious agents (multi-parameter screening).     

A challenge to the concept of tubal reflux to explain the rise and fall of CA125 in serum during the first trimester

Although amniotic fluid concentrations of cancer antigen (CA) 125 rise during the first two trimesters of pregnancy, the serum concentrations of CA125 peak during the first trimester and drop to non-pregnant values in the second and third trimester. A previous hypothesis to explain this phenomenon was that in the early first trimester decidual CA125 gains access to the maternal compartment via 'tubal reflux' and subsequent absorption by peritoneal lymphatics. However, as pregnancy advances, the decidua capsularis fuses with the decidua parietalis, thus obliterating the endometrial cavity at 10-12 weeks; the Fallopian tubes thus become functionally obstructed. To test this hypothesis, we evaluated early first trimester CA125 concentrations in women conceiving by in-vitro fertilization (IVF) and embryo transfer with patent tubes (group 1) and in those conceiving by IVF and embryo transfer with bilateral tubal occlusion (group 2). We also compared those conceiving with human menopausal gonadotrophin therapy for ovulation induction without assisted reproduction (group 3) and those conceiving without fertility drugs in assisted reproduction (group 4). Mean CA125 concentrations were similar in groups 1-3; the mean CA125 concentration in group 4 was lower but this difference was not statistically significant, probably due to the small sample size. These data do not support the concept that tubal reflux explains the rise and fall of serum concentrations of CA125, since these were equal in IVF conceptions with or without tubal patency.     

Comparison of two enzyme-linked immunosorbent assays and one rapid immunoblot assay for detection of herpes simplex virus type 2-specific antibodies in serum

The sensitivities and specificities of three immunoassays for the detection of herpes simplex virus type 2 (HSV-2)-specific immunoglobulin G antibodies in serum, including the one-strip rapid immunoblot assay (RIBA; Chiron Corporation) and two indirect enzyme immunosorbent assays (EIA; Gull Laboratories and Centocor), were compared by testing a panel of 1,250 serum samples from individuals attending an outpatient clinic for sexually transmitted diseases. A qualitative agreement among the three assays was observed with 1,080 serum samples (86.4%); 291 of the serum samples (23.3%) were positive, 789 samples (63.1%) were negative, and 170 serum samples (13.6%) gave a discordant result. Results were considered conclusive when a concordant result was obtained with two of three assays. The sensitivities and specificities of the RIBA, the Gull EIA, and the Centocor EIA proved to be 99.2, 99.7, and 89.9% and 97.1, 96.7, and 99.3%, respectively. These results indicate that the Chiron RIBA and the Gull EIA are especially useful and reliable for the detection of HSV-2-specific antibodies in serum.     

Can manipulation of a pelvic tumour influence the serum level of cancer antigen 125 and cancer-associated serum antigen?

Cancer antigen 125 (CA 125) and cancer-associated serum antigen (CASA) were measured in 24 women with pelvic masses before and after a gynaecological examination and ultrasonography. CA 125 decreased median 16% after manipulation (P < 0.0001) and CASA decreased median 8% (P = 0.0077). The decline was found in patients with benign tumours as well as in patients with malignant tumours.     

Preparation of respiratory syncytial virus subgroup A and B antigens for enzyme immunoassay antibody detection

A simplified method was described for purification of respiratory syncytial virus (RSV) subgroup A and B aimed to be used as antigens in enzyme immunoassay (EIA). The titer of each RSV subgroup and the amount of protein was determined from the visible band in 45% sucrose gradient. The quality of prepared RSV subgroup antigens for EIA was described in terms of the achievable final titer, the amount of protein, and EIA criss-cross titration. The RSV subgroup A and B antigens, diluted as 1:100 (low opalescent band in 45% sucrose layer) or 1:800 (high opalescent band in 45% sucrose layer) produced a positive reaction in EIA criss-cross titration with IgG antibodies from the patient's serum (convalescent phase) diluted as 1:25,600 (for RSV A) and 1:6,400 (for RSV B). This method offers shorter and more simplified steps of viral antigen purification, and provides acceptable quantity and quality of viral antigens appropriate for use in EIA.     

Are patients with cirrhotic stage primary sclerosing cholangitis at risk for the development of hepatocellular cancer?

Inhibin is an ovarian protein previously shown, using a nonspecific assay, to be elevated in serum of women with ovarian cancer. However, inhibin is secreted in multiple biochemical forms, including dimeric inhibin A and B and alpha inhibin precursors (pro-alphaC), each of which can now be specifically measured. We have examined the secretion of inhibin B and pro-alphaC inhibin in serum from women with epithelial ovarian cancer (EOC) for the first time, and have compared these analytes to inhibin A and total inhibin (inhibin A + B + pro-alphaC) as potential serum markers for EOC in postmenopausal women. Of all the immunoreactive inhibin proteins studied, the best serum marker was pro-alphaC, with 22% of women with EOC having levels that exceeded the range of values in women without EOC. Since CA 125 and pro-alphaC levels were not significantly correlated, combination of these markers resulted in 87% of EOC cases having elevated preoperative serum levels, a 9% increase over CA 125 alone. These data suggest that alpha inhibin secretion, especially pro-alphaC, may be useful in addition to CA 125 as a serum marker for EOC in postmenopausal women.     

Antigenic phenotypes common to rat oval cells, primary hepatocellular carcinomas and developing bile ducts

The shared expression of monoclonal antibody-defined antigens by oval cells and by bile ducts, neoplastic nodules and primary hepatocellular carcinomas (PHC) has provided support for the ability of oval cells to undergo differentiation along ductular or hepatocyte lineages and/or to progress to hepatocellular carcinoma. With the aim of obtaining additional insight into this process, we have combined serial section and double labeling immunofluorescence analysis to determine if phenotypes expressed in vitro by four rat oval cell lines and the H5D.61 hepatocellular carcinoma cell line and in situ by ethionine-induced primary hepatocellular carcinomas reproduce antigenic patterns occurring during normal liver development. Analysis using monoclonal antibodies specific for the oval cell antigens OV6 and OC.2 and hepatocyte markers HBD.1 and H.4 defined subpopulations in four oval cell lines and neoplastic hepatocytes in PHC and H5D.61 with OC.2-/OV6+ and OC.2+/OV6+ phenotypes. Cells with an OC2+/OV6- phenotype were rarely observed in cell lines or primary tumors. In contrast, areas composed of OV6+/H.4+ cells were frequently found in PHC. Examination of fetal and neonatal rat livers demonstrated the stage-specific appearance of three of these phenotypes during liver development. The OC.2+/OV6- phenotype appeared transiently prior to embryonic day (ED) 18 in a subpopulation of HBD.1+ hepatoblasts. OV6 expression was first detected at ED18 on developing bile ducts that were negative for OC.2. These newly formed ducts rapidly acquired OC.2, starting with ducts in the hilar region and spreading outward towards the periphery. This OC.2 expression gradient persisted in the newborn rat liver but became more skewed towards doubly positive cells, with OC.2-/OV6+ cells being found primarily in the periphery. Hepatocytes expressing both OV6 and H.4 were not observed in fetal liver but appeared in neonatal liver in close proximity to OV6+ interlobular ducts. From these findings, it was concluded that oval cells and PHC display phenotypes representing normal stages in liver development, suggesting that oval cells and cells within ethionine-induced PHC are capable of initiating but are unable to complete pathways of hepatocytic or biliary differentiation.     

Antigenicity of a synthetic peptide from glucosyltransferases of Streptococcus mutans in humans

Human salivary immunoglobulin A (IgA) and serum IgG antibodies to the Streptococcus mutans glucosyltransferases (Gtfs) and to a synthetic peptide of 19 amino acids from a conserved region in the Gtfs (residues 435 to 453) were determined in young adults by enzyme-linked immunosorbent assay. Varying levels of antibody to Gtfs were detected in saliva or serum, with significantly higher levels of antibody to GtfD than to GtfB/C or GtfC. Anti-Gtf IgA levels in saliva did not correlate with those of IgG in serum. Caries-free (CF) volunteers exhibited significantly higher salivary IgA antibody levels to the peptide and to GtfB/C or GtfC than did the caries-active (CA) subjects. Preincubation of CF saliva and serum with the peptide inhibited the antibodies to the Gtfs in a dose-dependent manner, whereas preincubation of the samples from the CA group resulted in only partial inhibition. Our results indicated that this 19-amino-acid peptide includes one of the major B-cell epitopes of Gtfs and that CF individuals have higher titers of antibodies than CA subjects.     

Serum concentrations of cancer antigen 125, placental alkaline phosphatase, cancer-associated serum antigen and free beta human chorionic gonadotrophin as prognostic markers for epithelial ovarian cancer

OBJECTIVE: To investigate the prognostic significance of elevated levels of cancer antigen 125 (CA125), placental alkaline phosphatase (PLAP), free beta human chorionic gonadotrophin (hCG) and cancer-associated serum antigen (CASA) in women with primary epithelial ovarian carcinoma. DESIGN: A two year follow up study of survival. SETTING: A tertiary care gynaecological oncology unit. PARTICIPANTS: One hundred and eleven women with histologically confirmed epithelial ovarian cancer. MAIN OUTCOME MEASURES: Survival over a two year period. RESULTS: Stage corrected log-rank chi 2 tests demonstrated a significant effect on survival for all four tumour markers (CA125 P = 0.0142; PLAP P < 0.0001; CASA P = 0.0098; hCG P = 0.0002). This was confirmed when each variable was fitted together with disease stage in Cox proportional hazard models. When fitted as multiple variables in a Cox proportional hazard model, the addition of free beta-hCG and CASA to disease stage, PLAP concentrations and CA125 levels did not demonstrate further prognostic value. CONCLUSIONS: Levels of all four markers correlate with survival in patients with epithelial ovarian cancer. The combination of PLAP and CA125 concentrations together with disease stage may be used to predict survival but the addition of hCG and CASA levels do not give additional prognostic information.     

Comparison of enzyme immunoassays for antibodies to Haemophilus ducreyi in a community outbreak of chancroid in the United States

The performance of two EIAs (adsorption EIA and lipooligosaccharide [LOS] EIA) that detect antibodies to Haemophilus ducreyi was evaluated with serum specimens obtained from 163 patients (96 with genital ulcer disease [GUD]). Paired serum specimens (initial and follow-up) were obtained from 52 of the GUD patients. By use of initial serum specimens from 82 GUD patients whose etiologic agents for their ulcers had been identified, the adsorption EIA had a sensitivity and specificity for chancroid of 53% and 71%, while the LOS EIA had a sensitivity and specificity of 48% and 89%, respectively. Sensitivity and specificity of the adsorption EIA increased to 78% and 84%, respectively, when the results of follow-up serum specimens were used to calculate optimal performance. The proportion of patients testing positive for H. ducreyi who had anti-H. ducreyi IgG antibodies, as determined by adsorption EIA, increased with the duration of infection, thus limiting the role of EIAs in the diagnosis of chancroid.