Overlapping but distinct roles for NOTCH receptors in human cardiovascular disease.

The NOTCH signalling pathway is an essential pathway, involved in many cellular processes, including cell fate decision, cell proliferation, and cell death and important in the development of most organs. Mutations in genes encoding components of the NOTCH signalling pathway lead to a spectrum of congenital disorders. Over the past decades, mutations in human NOTCH signalling genes have been identified in several diseases with cardiovascular involvement. NOTCH1 mutations have been described in bicuspid aortic valve disease, left-sided congenital heart disease, and Adams-Oliver syndrome. NOTCH2 mutations lead to the development of Alagille syndrome, while mutations in NOTCH3 cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. To date, mutations in NOTCH4 have not been associated with cardiovascular disease. This review focuses on the mutations described in NOTCH1, NOTCH2, and NOTCH3 and their associated cardiovascular phenotypes.

A patient with interstitial lung disease secondary to dermatomyositis: a case report and review of the literature.

We describe the case of a man with known dermatomyositis who presented with a dry cough and who early after admission rapidly evolved to respiratory insufficiency. Based on pathological and radiological findings, the diagnosis of diffuse alveolar damage was made. Postmortem examination also revealed infection with yeast, Torulopsis glabrata. Polymyositis (PM) and dermatomyositis (DM) are both auto-immune diseases, which are characterised by the presence of auto-antibodies and tissue-inflammation, mainly involving the muscles. Patients with PM/DM may have pulmonary complications, often responsible for higher morbidity and mortality. Interstitial lung disease can present itself in different shapes and forms (bronchiolitis obliterans organising pneumonia, non-specific organising pneumonia, usual interstitial pneumonia, acute interstitial pneumonia) and the diagnosis is made based on the combination of pathological examination and radiological findings.

Excessive eosinophilia as paraneoplastic syndrome in a patient with non-small-cell lung carcinoma: a case report and review of the literature.

Hypereosinophilia is a phenomenon which is associated with a broad variety of allergic, infectious, paraneoplastic and systemic diseases. Depending on the aetiology, these disorders differ in severity from self-limiting to life-threatening. Although it is well known that hypereosinophilia can occur in association with a solid tumour, exact numbers of incidence are lacking. We describe a patient with respiratory insufficiency and an elevated level of eosinophils in the peripheral blood. A diagnostic work-up revealed the presence of a disseminated non-small-cell carcinoma of the lung; an association not frequently described.

Necrotising sarcoid granulomatosis: clinical, functional, endoscopical and radiographical evaluations.

Necrotising sarcoid granulomatosis (NSG) is a rare disease diagnosed on the basis of pathological features. The present study reports the characteristics of 14 cases of NSG. The mean age at the appearance of first symptoms was 37 yrs and the mean delay between first symptoms and diagnosis was 1 yr. Extrarespiratory symptoms were more common (12 out of 14) than respiratory symptoms (eight out of 14). Seven patients had inflammatory syndrome. Bronchoalveolar lavage was performed in eight patients and found to be normal in three cases. Respiratory function was normal in 13 patients, but carbon monoxide diffusing capacity was slightly decreased in eight of the 11 patients tested. A computed tomography scan showed a solitary nodule in four out of 14 cases, bilateral nodules in three and infiltrates in seven. One patient died from neurological complications despite treatment with corticosteroids and immunosuppressive drugs. Two cases of relapse were observed in patients initially treated with corticosteroids, and there were two cases of relapse after surgery. No relapse occurred in the five untreated patients. During the follow-up, lung cancer was detected at 26 months and 8 yrs, respectively, after NSG diagnosis in two patients. In conclusion, no one treatment is associated with a better outcome than the others, although lung biopsy might be necessary in case of isolated nodule or cavitation. Greater vigilance is required during the follow-up.

Quality of intrapartum cardiotocography in twin deliveries.

OBJECTIVE: Intrapartum fetal heart rate (FHR) recordings in twins were compared for fetal signal loss during both stages of labor to assess the quality of these recordings by the method that had been used: external ultrasound or directly via a scalp electrode. STUDY DESIGN: Analysis of recordings collected between January 1, 1994, and January 1, 2002, from consecutive twin deliveries at the Vrije Universiteit Medical Center in Amsterdam. One hundred seventy-two twins that delivered via the vaginal route were included in the study. FHR recordings had a duration of at least 1 hour before the birth of the second twin. Subdivision took place on the basis of the recording technique, ie, ultrasound or scalp electrode. FHR data was obtained with HP-M1350 cardiotocographs. The status (pen on, pen off, maternal signal) and the mode of the signals were acquired. The duration of pen lifts and maternal signals was divided by the total duration of the recording. Statistical analyses were performed with the Mann-Whitney U test and the Wilcoxon signed ranks test. RESULTS: Recordings obtained via ultrasound demonstrated significantly more fetal signal loss than those obtained via the direct mode, particularly in the second stage. Approximately 26% to 33% of first stage and 41% to 63% of second stage ultrasound intrapartum FHR recordings in twins exceeded the International Federation of Gynecology and Obstetrics (FIGO) criteria for fetal signal loss. CONCLUSION: Intrapartum FHR monitoring via ultrasound provides far poorer quality FHR signals than the direct mode. The direct mode deserves a more prominent position in fetal surveillance than it currently has.

The quality of intrapartum fetal heart rate monitoring.

OBJECTIVE: To determine the quality of fetal heart rate (FHR) recordings during the first and second stage of labor by quantifying the amount of fetal signal loss in relation to the method of monitoring: external ultrasound or directly via a scalp electrode. STUDY DESIGN: Analysis of 239 intrapartum recordings stored between 1 January 2001 and 1 July 2001 from consecutive deliveries at the Vrije Universiteit Medical Center in Amsterdam. Singletons delivered via the vaginal route were included in the study. FHR recordings had duration of at least 1h prior to birth of the infant. Subdivision in three groups took place on the basis of the recording technique which had been used; i.e. ultrasound, scalp electrode or a combination of both methods. FHR data was obtained using HP-M1350 cardiotocographs. The status (pen on, pen off, maternal signal) and the mode of the signals were acquired. The duration of pen lifts and maternal signals was divided by the total duration of the recording. Statistical analyses were performed with the Mann-Whitney U-test and the Wilcoxon signed ranks test. RESULTS: Recordings obtained via ultrasound demonstrated significantly more fetal signal loss than those obtained via the direct mode, particularly in the second stage. The FIGO criteria for fetal signal loss with external ultrasound were not fulfilled during this stage for about half the cases. CONCLUSION: Intrapartum FHR monitoring via a scalp electrode provides far better quality FHR signals than external ultrasound and deserves a more prominent position in fetal surveillance than it currently has.

Antibody-dependent cell-mediated cytotoxicity can be induced by MUC1 peptide vaccination of breast cancer patients.

Human polymorphic epithelial mucin (PEM, MUC1) is a high molecular weight transmembrane glycoprotein expressed on the apical cell surface of glandular epithelium and is over-expressed and hypo-glycosylated in adenocarcinomas. The extracellular part of the molecule consists mainly of a variable number of 20 amino acid repeats that contain cryptic epitopes exposed in malignancy. The objective of our study was to determine whether humanized MUC1 MAbs and Abs induced by vaccination of breast cancer patients with MUC1 peptides can effect an antibody-dependent cell-mediated cytotoxicity (ADCC). An in vitro assay has been set up in which the breast tumor cell line ZR-75-1 is used as target and PBMC of healthy donors as effector cells. Different target and effector cells, as well as various MUC1 MAbs were tested to optimize the efficacy of the in vitro assay. The humanized MAb HuHMFG-1, which recognizes the PDTR sequence in the MUC1 tandem repeat, induced a strong cell-mediated cytotoxicity. Nine MUC1-expressing tumor cell lines, including 3 bone marrow-derived cell lines, as well as 2 MUC1-transfected cell lines were susceptible to different extent to MUC1 Ab-dependent killing. Large variations in the killing capacity of PBMC from healthy donors were found. The NK cells were the essential effector cells for the MUC1 Ab-dependent killing. Plasma samples with induced high levels of MUC1 Ab were obtained from breast cancer patients repeatedly immunized with a KLH-conjugated 33-mer or 106-mer MUC1 tandem repeat. Pre- and post-vaccinated plasma samples of these patients were compared in the ADCC assay and it could be clearly demonstrated that the induced MUC1 Abs can effect tumor cell killing. MUC1 Ab-dependent cell-mediated tumor cell killing may occur in vivo and the ADCC assay can be applied to monitor MUC1 vaccination trials.

Maternal serum Ca125 and Ca15-3 antigen levels in normal and pathological pregnancy.

OBJECTIVE: To evaluate the value of maternal serum CA125 and CA15-3 concentrations for discriminating pathological from normal pregnancies. METHODS: Serum samples from 120 women, in whom pregnancy outcome was pathological, i.e. spontaneous abortion, fetal death, intrauterine growth retardation, chromosomal and structural abnormalities, and (pre)eclampsia, were assessed for CA125 and CA15-3 and compared with levels found in 350 women with a normal pregnancy outcome matched for age and duration of pregnancy. RESULTS: Maternal CA125 serum values were significantly higher in the first and the third trimester of pregnancy (median 23.0 and 21.0 U/ml; p < 0.00001 and p < 0.001, respectively), compared to those in the second trimester (median 14.0 U/ml), but not significantly different from those obtained in pathological pregnancies. Maternal serum CA15-3 values were significantly higher during the third trimester (median 26.0 U/ml) compared to the first and second trimester of pregnancy (median 14.0 and 15.0 U/ml; p < 0.0001); CA15-3 serum levels in normal and pathological pregnancies showed no significant difference. CONCLUSION: Maternal serum levels of CA125 are higher during the first and third trimester of pregnancy. CA15-3 maternal serum levels are higher during the third trimester compared to the first and second trimester. Maternal CA125 and CA15-3 serum levels showed no relation with a pathological outcome of pregnancy.

Reactivity of natural and induced human antibodies to MUC1 mucin with MUC1 peptides and n-acetylgalactosamine (GalNAc) peptides.

Antibodies (Abs) to MUC1 occur naturally in both healthy subjects and cancer patients and can be induced by MUC1 peptide vaccination. We compared the specificity of natural and induced MUC1 Abs with the objective of defining an effective MUC1 vaccine for active immunotherapy of adenocarcinoma patients. Serum samples, selected out of a screened population of 492 subjects for their high levels of IgG and/or IgM MUC1 Abs, were obtained from 55 control subjects and from 26 breast cancer patients before primary treatment, as well as from 19 breast cancer patients immunized with MUC1 peptides coupled to keyhole limpet hemocyanin (KLH) and mixed with QS-21. The samples were tested with enzyme-linked immunoassays for reactivity with (1) overlapping hepta- and 20-mer peptides spanning the MUC1 tandem repeat sequence; (2) two modified 60-mer peptides with substitutions in the PDTR (PDTA) or in the STAPPA (STAAAA) sequence of each tandem repeat; and (3) four 60-mer glycopeptides with each 1, 2, 3 and 5 mol N-acetylgalactosamine (GalNAc) per repeat. More than one minimal epitopic sequence could be defined, indicating that Abs directed to more than one region of the MUC1 peptide core can coexist in one and the same subject. The most frequent minimal epitopic sequence of natural MUC1 IgG and IgM Abs was RPAPGS, followed by PPAHGVT and PDTRP. MUC1 peptide vaccination induced high titers of IgM and IgG Abs predominantly directed, respectively, to the PDTRPAP and the STAPPAHGV sequences of the tandem repeat. Natural MUC1 Abs from breast cancer patients reacted more strongly with the N-acetylgalactosamine (GalNAc) peptides than with the naked 60-mer peptide, while reactivity with the GalNAc-peptides was significantly reduced (2-tailed p < 0.0001) in the MUC1 IgG and IgM Abs induced by MUC1 peptide vaccination. Whereas in cancer patients glycans appear to participate in epitope conformation, the epitope(s) recognized by MUC1 Abs induced by peptide vaccination are already masked by minimal glycosylation. Therefore, our results indicate that a MUC1 glycopeptide would be a better vaccine than a naked peptide.

Survival in early breast cancer patients is favorably influenced by a natural humoral immune response to polymorphic epithelial mucin.

PURPOSE: Polymorphic epithelial mucin (PEM or MUC1) is being studied as a vaccine substrate for the immunotherapy of patients with adenocarcinoma. The present study analyzes the incidence of naturally occurring MUC1 antibodies in early breast cancer patients and relates the presence of these antibodies in pretreatment serum to outcome of disease. MATERIALS AND METHODS: We measured immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies to MUC1 with an enzyme-linked immunoassay (PEM.CIg), which uses a MUC1 triple-tandem repeat peptide conjugated to bovine serum albumin, in pretreatment serum samples obtained from 154 breast cancer patients (52 with stage I disease and 102 with stage II) and 302 controls. The median disease-specific survival time of breast cancer patients was 74 months (range, 15 to 118 months). A positive test result was defined as MUC1 IgG or IgM antibody levels equal to or greater than the corresponding rounded-up median results obtained in the total breast cancer population. RESULTS: A positive test result for both MUC1 IgG and IgM antibodies in pretreatment serum was associated with a significant benefit in disease-specific survival in stage I and II (P =.0116) breast cancer patients. Positive IgG and IgM MUC1 antibody levels had significant additional prognostic value to stage (P =.0437) in multivariate analysis. Disease-free survival probability did not differ significantly. However, stage II patients who tested positive for MUC1 IgG and IgM antibody and who relapsed had predominantly local recurrences or contralateral disease, as opposed to recurrences at distant sites in the patients with a negative humoral response (P =.026). CONCLUSION: Early breast cancer patients with a natural humoral response to MUC1 have a higher probability of freedom from distant failure and a better disease-specific survival. MUC1 antibodies may control hematogenic tumor dissemination and outgrowth by aiding the destruction of circulating or seeded MUC1-expressing tumor cells. Vaccination of breast cancer patients with MUC1-derived (glyco)peptides in an adjuvant setting may favorably influence the outcome of disease.

Human MUC1 mucin: a multifaceted glycoprotein.

Human MUC1 mucin, a membrane-bound glycoprotein, is a major component of the ductal cell surface of normal glandular cells. MUC1 is overexpressed and aberrantly glycosylated in carcinoma cells. The role MUC1 plays in cancer progression represents two sides of one coin: on the one hand, loss of polarity and overexpression of MUC1 in cancer cells interferes with cell adhesion and shields the tumor cell from immune recognition by the cellular arm of the immune system, thus favoring metastases; on the other hand, MUC1, in essence a self-antigen, is displaced and altered in malignancy and induces immune responses. Tumor-associated MUC1 has short carbohydrate sidechains and exposed epitopes on its peptide core; it gains access to the circulation and comes into contact with the immune system provoking humoral and cellular immune responses. Natural antibodies to MUC1 present in the circulation of cancer patients may be beneficial to the patient by restricting tumor growth and dissemination: early stage breast cancer patients with a humoral response to MUC1 have a better disease-specific survival. Several MUC1 peptide vaccines, differing in vectors, carrier proteins and adjuvants, have been tested in phase I clinical trials. They are capable of inducing predominantly humoral responses to the antigen, but evidence that these immune responses may be effective against the tumor in humans is still scarce.

Cellular and humoral immune responses to MUC1 mucin and tandem-repeat peptides in ovarian cancer patients and controls.

The objective of this study was to demonstrate the presence of proliferative T cell responses to human polymorphic epithelial mucin (MUC1) and its tandem-repeat peptides in peripheral blood mononuclear cells (PBMC) from ovarian cancer patients and from controls and to correlate these cellular responses to a humoral response to MUC1. PBMC were obtained from 6 healthy women, from 13 women in the third trimester of pregnancy and from 21 ovarian cancer patients. Only 1 of the 6 healthy women showed a weak primary proliferative response (stimulation index, SI <2) to a 20-mer MUC1 tandem-repeat peptide in the presence of interleukin-2 (IL-2). In PBMC from 5/13 pregnant women (38%) a weak response could be induced by the 20-mer and/or 60-mer tandem-repeat peptides (SI < or =3.0) and in PBMC from 8/15 ovarian cancer patients (53%) 20-mer and/or 60-mer MUC1 tandem-repeat peptides induced primary responses (SI < or =5.4). MUC1 mucin purified from a breast tumor cell line and/or from urine of a healthy donor had a relatively strong stimulating effect (SI < or =19) on PBMC from 4 of 16 ovarian cancer patients (25%). In contrast, in PBMC of 9 ovarian cancer patients stimulated by the addition of a Candida albicans extract, MUC1 mucin strongly inhibited proliferation. This inhibition could partially be abrogated by the addition of IL-2. MUC1 (CA 15.3 assay) and free circulating MUC1 IgG and IgM antibodies (PEM.CIg assay) were determined in the plasma of all subjects. The MUC1 and the free circulating MUC1 IgG antibody plasma levels were significantly higher in the ovarian cancer patients than in the healthy women. Although no significant correlations were found between MUC1 mucin, MUC1 Ab plasma levels and the individual proliferative responses to the MUC1 antigens, an association may exist between them, since all three are significantly higher in the ovarian cancer patients than in the healthy women.

Estimation of probability of malignancy using a logistic model combining physical examination, ultrasound, serum CA 125, and serum CA 72-4 in postmenopausal women with a pelvic mass: an international multicenter study.

BACKGROUND: To assess the differential diagnostic potential of physical examination, ultrasound, the serum CA 125 assay, and serum CA 72-4 assay, and the contribution of each parameter to a logistic model predicting the probability of malignancy in postmenopausal patients presenting with a pelvic mass. PATIENTS AND METHODS: In a multicenter, prospective study a total of 155 patients were evaluated preoperatively using a standard protocol for pelvic examination, transvaginal (occasionally additional abdominal) ultrasound, and serum CA 72-4 (cutoff level 3 U/ml) and CA 125 (cutoff level 35 U/ml). RESULTS: Fifty-nine malignant (39%) and 92 benign (61%) pelvic tumors were found in addition to 4 borderline tumors (3%). Forty-three patients appeared to have ovarian carcinoma, FIGO Stage III or IV in 28 cases. Borderline tumors were excluded from the statistical calculations. The diagnostic accuracy of each single parameter, i.e., pelvic examination, ultrasound, and serum CA 125 and CA 72-4 in discriminating between benign and malignant pelvic masses gave highly similar results (81, 76, 78, and 81% respectively). Best sensitivity was found in pelvic examination (92%); best specificity was found in CA 72-4 (93%). Using logistic regression analysis the power of pelvic examination appeared to be the most relevant (adjusted odds ratio 12.1), followed by ultrasound (odds ratio 9.7), serum CA 125 (odds ratio 5.0), and serum CA 72-4 (odds ratio 4.9). Age appeared to be nonpredictive. The logistic model gives a correct prediction in 87% of all cases. CONCLUSIONS: The addition of serum CA 72-4 to the combination of pelvic examination, ultrasound, and serum CA 125 leads to an improved discrimination between malignant and benign pelvic masses.

An enzyme-linked immunosorbent assay for the measurement of circulating antibodies to polymorphic epithelial mucin (MUC1).

INTRODUCTION: About one-third of breast and ovarian carcinoma patients have circulating antibodies reactive with polymorphic epithelial mucin (MUC1), either free or bound to immune complexes. While the presence of these immune complexes has prognostic significance in breast cancer patients, the significance of free MUC1 antibodies is less clear. The objective of this study was to develop a reliable assay for the accurate determination of circulating free antibodies to MUC1. MATERIAL AND METHODS: We developed an enzyme-linked immunosorbent assay (ELISA) (PEM.CIg) employing a 60 mer peptide (a triple tandem repeat sequence of the MUC1 peptide core) conjugated to bovine serum albumin and peroxidase-labeled antihuman immunoglobulin G or M antibodies. The assay was standardized and its analytical performance evaluated. A total of 492 serum samples were obtained from 40 healthy men, from 201 healthy women (including 55 women without a history of pregnancy and 45 pregnant women), and (before primary treatment) from 62 benign breast tumor patients and 190 breast cancer patients. MUC1 serum levels were determined with commercial CA 15-3 tests. RESULTS: Circulating antibodies to MUC1 are present both in healthy subjects and in breast cancer patients. The within- and between-assay coefficients of variation were, respectively, 2 and 12% for the IgG determinations and 1.2 and 3% for the IgM determinations. Correlation coefficients for serially diluted serum samples ranged from 0.9998 to 0.9920 for IgG and from 0.9996 to 0.9818 for IgM determinations. The reactivity of serum samples was partially blocked by the addition of various MUC1 peptides and by MUC1 mucin. The inhibiting effect of modified 60 mer peptides suggests the presence of antibodies directed to more than one epitope. CONCLUSIONS: The PEM. CIg assay is a reliable ELISA for measuring free MUC1 antibodies in serum. We are in the process of relating the results obtained in the breast cancer group to disease outcome to evaluate its prognostic significance. In addition, the assay may become a useful tool for vaccine therapy monitoring.

Humoral immune response to polymorphic epithelial mucin (MUC-1) in patients with benign and malignant breast tumours.

To investigate the clinical significance of an immune response to the MUC-1 encoded polymorphic epithelial mucin (PEM) breast cancer, circulating immune complexes containing PEM (PEM.CIC) were measured in sera from 96 healthy women, in pretreatment serum samples from 40 patients with benign breast tumours and from 140 patients with breast cancer and in serum samples from 61 breast cancer patients with recurrent or progressive disease. PEM.CIC were measured using a sandwich enzyme-linked immunoassay, and PEM serum levels were measured with CA 15.3 IRMA (Centocor Inc., Malvern, Pennsylvania, U.S.A.). Cut-off levels used for PEM.CIC and CA 15.3 were 120 Optical Density Units (O.D.) x 10(3) and 30 U/ml, respectively. In benign tumours, positivity for PEM.CIC was 37.5% (15/40). 36 of the 140 patients (25.7%) in the breast cancer pretreatment group had elevated PEM.CIC values. In patients with advanced metastatic disease, positivity for PEM.CIC was 18% (11/61). PEM.CIC was elevated in 32% (24/74) of node-negative patients, but only in 20% (12/59) of node-positive patients and absolute values were higher in node-negative patients (Mann-Whitney U test, two-tailed P = 0.0168). There was an inverse correlation between positivity for PEM.CIC and extent of disease: while 3 of the 6 patients with a carcinoma in situ were positive, only 1 of the 15 patients with more than five nodes involved had elevated levels of PEM.CIC. All 7 patients with distant metastases at first diagnosis were PEM.CIC negative. 28 out of 133 patients had a recurrence during the observation period (median 55 months, range 27-84 months). 23 of these 28 patients (82%) were PEM.CIC negative at the moment of first diagnosis. None of the patients with pretreatment elevation of both PEM.CIC and CA 15.3 (n = 13) relapsed. Our preliminary clinical results suggest that a humoral immune response to PEM protects against disease progression, and further support the idea of using synthetic peptides or glycopeptides containing the immunogenic core of the mucin as cancer vaccines.

Mucin-like carcinoma-associated antigen serum levels in patients with adenocarcinomas originating from ovary, breast and colon.

The mucin-like carcinoma-associated antigen (MCA) enzyme immunoassay was tested in 962 healthy controls. MCA levels were compared with CA 125 in 70 patients with benign and 76 with malignant ovarian tumors. In addition MCA was compared with CA 15.3 in 58 patients with breast cancer and with CEA in 50 patients with colon carcinoma. In healthy controls the 95th percentile cutoff of 19.2 U/ml appeared to be higher than generally used. With the common cutoff value of 14 U/ml, a 38% sensitivity and 100% specificity was reached in malignant versus benign ovarian tumors. In colorectal cancer only 4% of patients had elevated MCA serum levels (CEA: 50%). In breast cancer patients the MCA assay performed better than CA 15.3 although only 17.2% showed elevated levels (CA 15.3: 7.4%). Thus MCA seems to be of limited value in the diagnosis and follow-up of adenocarcinomas of breast, ovary or colon.

Polymorphic epithelial mucin (MUC-1)-containing circulating immune complexes in carcinoma patients.

Circulating immune complexes (CICs) containing polymorphic epithelial mucin (PEM/MUC-1) were found in sera of 24.5% of 151 primary breast carcinoma patients and 18-21.4% of patients with advanced ovarian (n = 56) and breast carcinomas (n = 61), 37% of patients with benign breast tumours, but in only 2.1% of 96 healthy individuals. The incorporation of PEM into CICs affects the detection of circulating PEM in commercial immunoassays such as the CA 15-3 assay, as suggested by a negative correlation between levels of PEM-containing immune complexes (PEM-CICs) and CA 15-3 values, and confirmed by isolation of PEM from CA 15-3-negative sera containing high levels of PEM-CICs. The amounts of PEM masked by human antibodies correspond to significant values of the CA 15-3 assay when monitoring patients for carcinoma. Most antibodies in PEM-CICs were of IgG class, suggesting their specific nature to the PEM epitopes.

The second generation CA 125 assays.

Optimal management of ovarian cancer patients can only be provided using the CA 125 serum test for treatment monitoring, early prediction of outcome and early detection of recurrence. The newly introduced second generation CA 125 assays, the Centocor CA 125 II IRMA, the Boehringer Mannheim Enzymun CA 125 II and the BYK Liamat CA 125 II are one-step heterlogous double-determinant solid phase assays that utilize the M11 as capture antibody and the original OC 125 as tracer. The CA 125 II assays will probably replace the original CA 125 assays within a short period of time. For comparison reasons the Abbot IMx CA 125 assay was also included in this study. Highly similar CA 125 distribution patterns were obtained with these new CA 125 II assays. Linear regression analysis in ovarian cancer patients showed the following: Centocor CA 125 II = 0.98 x CA 125 IRMA + 10.7 (r = 0.8717, P < 0.0001), Syx = 89.9; Enzymun CA 125 II = 1.03 x CA 125 + 9.0 (r = 0.8988, P < 0.0001) Syx = 81.8; BYK Liamat CA 125 II = 1.17 x CA 125 IRMA + 0.6 (r = 0.8930, P < 0.0001), Syx = 96.8. Our first technical and clinical evaluation of these three new CA 125 II assays shows their superior analytical performance, in addition to a high qualitative and quantitative correlation with the original CA 125 IRMA.