Tumor Antigen Nb/70K and Ca 125 Levels in the Blood of Preoperative Ovarian Cancer Patients and Controls: A Preliminary Report of the use of the Nb12123 and Ca 125 Radioimmunoassays Alone and in Combination

The NB12123 and CA125 radioimmunoassays, murine monoclonal antibody assays for measuring circulating levels of human ovarian tumor associated antigens NB/70K and CA 125, respectively, have been previously described. In the present study, preoperative serum samples were obtained from patients undergoing laparotomy for benign neoplastic ovarian tumors (N = 16), cancer of the cervix (N = 22), cancer of the uterus (N = 20), and cancer of the ovary (N = 47). Controls (N = 50) were obtained from healthy blood bank donors. No correlation was observed between the levels of NB/70K and CA 125 in these samples (r2 = .079, linear regression analysis). In general, increasing levels of both antigens were present with increasing tumor burden and higher histological grade. In addition, both markers were most elevated in the serum of ovarian cancer patients with serous and unclassified adenocarcinomas. Using 40 AU and 35 unit cut-offs for the NB/70K and CA 125 assay, respectively, overall specificity for healthy controls and patients with benign diseases approaches 100%. The combined sensitivity of the assays for ovarian cancer patient sera in this study indicates that the assays may be helpful in establishing a pre operative diagnosis of ovarian cancer. Complementarity of the NB/70K and CA 125 assays has been demonstrated, indicating that one or both assays may be used to monitor as many as 85% of ovarian cancer patients.

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OVX1 radioimmunoassay complements CA-125 for predicting the presence of residual ovarian carcinoma at second-look surgical surveillance procedures.

Journal of Clinical Oncology ◽

10.1200/jco.1993.11.8.1506 ◽

1993 ◽

Vol 11 (8) ◽

pp. 1506-1510 ◽

Cited By ~ 34

Author(s):

F J Xu ◽

Y H Yu ◽

L Daly ◽

K DeSombre ◽

L Anselmino ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Elevated Serum ◽

Ca 125 ◽

Serum Samples ◽

Persistent Disease ◽

Second Look ◽

Normal Individuals ◽

Positive Results ◽

Apparently Healthy

PURPOSE At second-look surgical surveillance procedures, normal CA-125 levels can be associated with persistent disease in 50% to 60% of patients. A novel radioimmunoassay (RIA) has been evaluated for the ability to identify patients with persistent disease who have normal levels of CA-125. MATERIALS AND METHODS The OVX1 double-determinant assay used a murine monoclonal antibody to detect an epitope on a high-molecular weight mucin-like glycoprotein. RESULTS Apparently healthy individuals had serum OVX1 levels of 2.23 +/- 2.48 U/mL (mean +/- SD). Elevated serum OVX1 levels (> 7.2 U/mL) were found in 5% of 184 normal individuals and in 70% of 93 epithelial ovarian cancer patients with clinically evident disease. Among sera from these ovarian cancer patients, OVX1 was elevated in 68% of 76 samples with CA-125 levels more than 35 U/mL and in 76% of 17 samples with CA-125 levels less than 35 U/mL. In serum samples obtained at the time of positive second-look laparotomy, 59% of 41 patients with CA-125 levels less than 35 U/mL had elevated OVX1 antigen levels, whereas 41% of 22 patients with CA-125 levels more than 35 U/mL had elevated serum OVX1 levels. In patients with negative second-look laparotomies, false-positive results were eliminated by increasing the threshold of OVX1 to 10.5 U/mL. At this level, 32% of 41 patients with positive second-look operations had an elevated OVX1 level, despite a normal CA-125 level. When used in combination, CA-125 (> 35 U/mL) and OVX1 (> 10.5 U/mL) detected persistent disease in 56% of 63 patients with positive surveillance procedures, compared with 35% when CA-125 was used alone (P < .05). CONCLUSION An elevated OVX1 level can alert oncologists to the possibility that ovarian cancer has persisted, despite the return of CA-125 to a normal range.

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Secretome Identifies Tenascin-X as a Potent Marker of Ovarian Cancer

BioMed Research International ◽

10.1155/2015/208017 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Marianne Kramer ◽

Sandra Pierredon ◽

Pascale Ribaux ◽

Jean-Christophe Tille ◽

Patrick Petignat ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cancer Patients ◽

Ca 125 ◽

Ovarian Cancer Cells ◽

Serous Ovarian Cancer ◽

Protein Biomarkers ◽

Serum Samples ◽

Cancer Tissues

CA-125 has been a valuable marker for the follow-up of ovarian cancer patients but it is not sensitive enough to be used as diagnostic marker. We had already used secretomic methods to identify proteins differentially secreted by serous ovarian cancer cells compared to healthy ovarian cells. Here, we evaluated the secretion of these proteins by ovarian cancer cells during the follow-up of one patient. Proteins that correlated with CA-125 levels were screened using serum samples from ovarian cancer patients as well as benign and healthy controls. Tenascin-X secretion was shown to correlate with CA-125 value in the initial case study. The immunohistochemical detection of increased amount of tenascin-X in ovarian cancer tissues compared to healthy tissues confirms the potent interest in tenascin-X as marker. We then quantified the tenascin-X level in serum of patients and identified tenascin-X as potent marker for ovarian cancer, showing that secretomic analysis is suitable for the identification of protein biomarkers when combined with protein immunoassay. Using this method, we determined tenascin-X as a new potent marker for serous ovarian cancer.

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Multicenter evaluation of human placental alkaline phosphatase as a possible tumor-associated antigen in serum.

Clinical Chemistry ◽

10.1093/clinchem/34.10.1995 ◽

1988 ◽

Vol 34 (10) ◽

pp. 1995-1999 ◽

Cited By ~ 34

Author(s):

M E De Broe ◽

D E Pollet

Keyword(s):

Ovarian Cancer ◽

Alkaline Phosphatase ◽

Testicular Cancer ◽

Cancer Patients ◽

Solid Phase ◽

Ca 125 ◽

Placental Alkaline Phosphatase ◽

Serum Samples ◽

Heavy Smoking ◽

Human Placental Alkaline Phosphatase

Abstract Using a solid-phase monoclonal antibody enzyme immuno-assay, we evaluated in a multicenter study (18 laboratories) the utility of evaluating catalytic activity of human placental alkaline phosphatase (hPLAP, EC 3.1.3.1) in serum as a potential tumor marker. We determined hPLAP in serum samples from 130 patients with ovarian cancer, 79 patients with testicular cancer (53 seminoma testis, 26 nonseminoma testis), 537 patients with various other malignant diseases (95 lung, 39 gastrointestinal, 195 breast, 208 others), 291 patients with benign diseases, and 213 healthy controls. To assess the influence of smoking on hPLAP activity in serum, we evaluated 79 serum samples from patients with noncancerous diseases for whom smoking habits had been recorded. Our main findings are: (a) hPLAP activity is frequently increased (greater than 100 mU/L) in pre-operative serum samples from ovarian cancer patients (49%) and from testicular cancer patients (59% overall; 72% seminoma, 35% nonseminoma); (b) heavy smoking may increase hPLAP activity; (c) excluding heavy smokers, a 96% specificity for cancerous lesions was observed; (d) in patients with ovarian malignancies, CA 125 and hPLAP may behave as independent markers; and (e) in patients with seminoma, hPLAP is clearly more frequently increased than is beta-choriogonadotropin.

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Monitoring cancer antigen 125 in serum of ovarian cancer patients after administration of 131I-labeled F(ab')2 fragments of OC125 antibody

Clinical Chemistry ◽

10.1093/clinchem/39.5.891 ◽

1993 ◽

Vol 39 (5) ◽

pp. 891-896 ◽

Cited By ~ 15

Author(s):

J Reinsberg ◽

B Schultes ◽

U Wagner ◽

D Krebs

Keyword(s):

Ovarian Cancer ◽

Enzyme Immunoassay ◽

Cancer Patients ◽

False Positive ◽

Repeated Administration ◽

Ca 125 ◽

Cancer Antigen 125 ◽

Serum Samples ◽

Cancer Antigen ◽

Apparent Increase

Abstract We evaluated the effect of repeated administration of OC125 F(ab')2 fragments on cancer antigen (CA) 125 determination in 210 serum samples from 30 patients. We found falsely high CA 125 concentrations in 142 (68%) samples, using a homologous CA 125 enzyme immunoassay (EIA) with OC125 antibodies. The Truquant OV2 method, which involves two other murine antibodies, and the IMx CA 125 method, which uses sheep antibodies as capture antibodies, resulted in only slightly increased (false-positive) values in some samples with exceptionally high CA 125 EIA values. We measured falsely low CA 125 values in 37 (18%) samples with the Truquant OV2 method. Interferences could be eliminated by removal of serum IgG. Our results suggest that interferences are to some extent caused by anti-idiotypic IgG induced by OC125 administration. Assays involving nonmurine anti-CA 125 antibodies as capture antibodies seem to be most suited for CA 125 determination after OC125 treatment, but in every case an apparent increase of CA 125 after OC125 infusion should be validated.

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Early Modeled Longitudinal CA-125 Kinetics and Survival of Ovarian Cancer Patients: A GINECO AGO MRC CTU Study

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-18-3335 ◽

2019 ◽

Vol 25 (17) ◽

pp. 5342-5350 ◽

Cited By ~ 8

Author(s):

Olivier Colomban ◽

Michel Tod ◽

Alexandra Leary ◽

Isabelle Ray-Coquard ◽

Alain Lortholary ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Ca 125

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Automated Assay of a Four-Protein Biomarker Panel for Improved Detection of Ovarian Cancer

Cancers ◽

10.3390/cancers13020325 ◽

2021 ◽

Vol 13 (2) ◽

pp. 325

Author(s):

Christopher Walker ◽

Tuan-Minh Nguyen ◽

Shlomit Jessel ◽

Ayesha B. Alvero ◽

Dan-Arin Silasi ◽

...

Keyword(s):

Ovarian Cancer ◽

Early Detection ◽

Predictive Value ◽

Early Stage ◽

Ca 125 ◽

Healthy Controls ◽

Classification Models ◽

Serum Samples ◽

Protein Biomarker ◽

Biomarker Panel

Background: Mortality from ovarian cancer remains high due to the lack of methods for early detection. The difficulty lies in the low prevalence of the disease necessitating a significantly high specificity and positive-predictive value (PPV) to avoid unneeded and invasive intervention. Currently, cancer antigen- 125 (CA-125) is the most commonly used biomarker for the early detection of ovarian cancer. In this study we determine the value of combining macrophage migration inhibitory factor (MIF), osteopontin (OPN), and prolactin (PROL) with CA-125 in the detection of ovarian cancer serum samples from healthy controls. Materials and Methods: A total of 432 serum samples were included in this study. 153 samples were from ovarian cancer patients and 279 samples were from age-matched healthy controls. The four proteins were quantified using a fully automated, multi-analyte immunoassay. The serum samples were divided into training and testing datasets and analyzed using four classification models to calculate accuracy, sensitivity, specificity, PPV, negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). Results: The four-protein biomarker panel yielded an average accuracy of 91% compared to 85% using CA-125 alone across four classification models (p = 3.224 × 10−9). Further, in our cohort, the four-protein biomarker panel demonstrated a higher sensitivity (median of 76%), specificity (median of 98%), PPV (median of 91.5%), and NPV (median of 92%), compared to CA-125 alone. The performance of the four-protein biomarker remained better than CA-125 alone even in experiments comparing early stage (Stage I and Stage II) ovarian cancer to healthy controls. Conclusions: Combining MIF, OPN, PROL, and CA-125 can better differentiate ovarian cancer from healthy controls compared to CA-125 alone.

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High serum and ascitic soluble interleukin-2 receptor alpha levels in advanced epithelial ovarian cancer [see comments]

Blood ◽

10.1182/blood.v81.2.424.424 ◽

1993 ◽

Vol 81 (2) ◽

pp. 424-429 ◽

Cited By ~ 33

Author(s):

DP Barton ◽

DK Blanchard ◽

B Michelini-Norris ◽

SV Nicosia ◽

D Cavanagh ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Cancer Patients ◽

Ascitic Fluid ◽

Total Protein ◽

Interleukin 2 ◽

Serum Levels ◽

Ca 125 ◽

Soluble Interleukin 2 Receptor ◽

Advanced Epithelial Ovarian Cancer

Abstract This study was undertaken to determine if advanced epithelial ovarian cancer was associated with increased serum and ascitic levels of soluble interleukin-2 receptor alpha (sIL-2R alpha). Serum and ascitic fluid samples from 23 ovarian cancer patients were analyzed for sIL-2R alpha using an enzyme-linked immunosorbent assay and compared with the serum and peritoneal levels in 18 normal females. The samples were analyzed for CA-125 levels using a radioimmunoassay and the total protein was also measured. Normal individuals had low serum levels of sIL-2R alpha (367.5 +/- 44.6 U/mL), with similar levels of sIL-2R alpha in the normal peritoneal fluid (438.6 +/- 48.8 U/mL). In contrast, the serum and ascitic fluid levels in ovarian cancer patients were significantly higher (746.7 +/- 82.9 U/mL, P = .0006; 2,656.7 +/- 373.7 U/mL, P = .00002, respectively). The results for sIL-2R alpha were also significant when the levels were expressed per milligram of total protein. More importantly, in almost every ovarian cancer patient the ascitic sIL-2R alpha level far exceeded the serum level, a pattern also observed for CA-125. There was no correlation between the serum and ascitic sIL-2R alpha levels, or between the serum and ascitic CA-125 levels. Although the serum levels of sIL-2R alpha and CA-125 were elevated in the same patient, overall there was no correlation between the serum sIL-2R alpha and serum CA-125 levels, either when the levels were expressed in absolute units or per milligram of total protein. Similarly, there was no correlation between sIL-2R alpha and CA-125 levels in individual ascitic samples. While CA-125 levels may reflect an independent index of tumor burden, these results suggest that selective accumulation of sIL-2R alpha in the ascites may be one of the factors associated with the known nonresponsiveness of the infiltrating lymphocytes against ovarian carcinoma cells.

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Phase II study of vinorelbine in patients with pretreated advanced ovarian cancer: activity in platinum-resistant disease.

Journal of Clinical Oncology ◽

10.1200/jco.1996.14.9.2546 ◽

1996 ◽

Vol 14 (9) ◽

pp. 2546-2551 ◽

Cited By ~ 104

Author(s):

E Bajetta ◽

A Di Leo ◽

L Biganzoli ◽

L Mariani ◽

F Cappuzzo ◽

...

Keyword(s):

Ovarian Cancer ◽

Confidence Interval ◽

Cancer Patients ◽

Response Rate ◽

Advanced Ovarian Cancer ◽

Dose Intensity ◽

Ca 125 ◽

Resistant Disease ◽

Platinum Resistant ◽

Exact Confidence Interval

PURPOSE The aim of the study was to evaluate the activity of vinorelbine (VNLB) in a population of advanced ovarian cancer patients, with particular attention to defining its role in platinum-resistant disease. PATIENTS AND METHODS Thirty-three patients were recruited and treated with VNLB 25 mg/m2 intravenously (IV) weekly. the median age was 53 years, performance status 0 to 2, and number of previous chemotherapy regimens two (range, one to five). Twenty-four patients were platinum-resistant; the remaining nine either were platinum-sensitive (four cases) or had undetermined sensitivity (five cases). RESULTS The mean delivered dose-intensity of VNLB was 67% of the planned level, because 60% of the cycles were delayed due to neutropenia or anemia. Four partial responses (PRs) and one complete response (CR) were observed, for an overall response rate of 15% (95% exact confidence interval, 5.1% to 31.9%). All the responses occurred in the subgroup of 24 platinum-resistant cases, in whom the response rate was 21% (95% exact confidence interval, 7.1% to 42.1%). Seven patients became stabilized on VNLB, and 27% of the cases showed a reduction in serum cancer antigen 125 (CA 125) levels. G3/G4 side effects consisted of neutropenia, anemia, and worsening of preexisting peripheral neuropathy. No treatment-related deaths occurred. CONCLUSION VNLB led to a 21% response rate in the population of heavily pretreated and platinum-resistant ovarian cancer patients. Further studies of VNLB alone or in combination with taxanes are warranted in patients with less pretreatment.

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Comparison of clinico-pathological characteristics and survival of recurrent ovarian cancer patients on seven different chemo-protocols

Acta Pharmaceutica ◽

10.2478/acph-2019-0002 ◽

2019 ◽

Vol 69 (1) ◽

pp. 87-97

Author(s):

Saima Sattar ◽

Mobasher Ahmad ◽

Hamid Saeed ◽

Zikria Saleem ◽

Zeeshan Danish ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Histological Grade ◽

Progression Free Survival ◽

Complete Response ◽

Recurrent Ovarian Cancer ◽

Figo Stage ◽

Care Hospital ◽

Pathological Characteristics ◽

Literature Evidence

Abstract Despite growing prevalence of ovarian cancer (OC) in Pakistan, no literature evidence exists regarding its clinic-pathological characteristics, survival and compliance of patients with recurrent ovarian cancer on various chemo-protocols. An observational study was conducted by enrolling 251 recurrent OC patients on 7 different chemo-protocols, from a specialized cancer care hospital, Lahore, Pakistan, using convenient judgmental sampling. The study was conducted for a period of 6 months. Most of the patients were between 18 and 70 years of age, with IIIC FIGO stage and papillary serous histological grade. As per RECIST, improved partial response (PR) (63.3 %) and complete response (CR) (52.1 %) was observed in the CP (carboplatin + paclitaxel) arm, substantiated by improved median progression free survival (PFS) and overall survival (OS) in CP and CD (carboplatin + docetaxel) arms, respectively, yet with no significant differences in survival curves, PFS (p = 0.12) and OS (p = 0.22). Interestingly, the highest and the lowest patient non-compliance were observed in CG (carboplatin + gemcitabine) (81.6 %) and paclitaxel (4.5 %) arms, resp. As per the hazard model for survival, topotecan showed significant association with the therapy related events/deaths compared to other protocols. These data suggest that CP regimen exhibited improved clinical efficacy and decreased toxicity related non-compliance in recurrent ovarian cancer patients of Lahore.

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