The prognostic value of early CA125 serum assay in epithelial ovarian carcinoma.

We examined the prognostic value of early serum CA125 assay in 58 patients with advanced epithelial ovarian cancer together with residual disease, age, tumour grade, performance status, and the presence of ascites or adhesions at primary surgery. CA125 was a highly significant predictor of both progression free and overall survival after the first cycle and throughout primary chemotherapy. After the first cycle, CA125 was by far the most significant predictor of progression free survival (P < 0.0005). At this time, CA125 was a highly significant predictor of survival (P < 0.005), but did not add to performance status (P < 0.001) in multivariate analysis. We were able to identify three statistically-distinct prognostic groups. Patients in the upper quartile, with CA125 levels greater than 450 U ml-1, had a very poor median survival of 7 months. Patients in the lower quartile, with CA125 levels less than 55 U ml-1 had a good median survival of 23 months. Those in the two interquartile groups, who had CA125 levels ranging from 58-221 U ml-1 and 228-434 U ml-1, had relatively intermediate median survival times of 16 months and 15 months respectively. Although CA125 levels provided significant prognostic information, in the majority of patients CA125 merely confirmed overall clinical impression.

An assessment of the clinical usefulness of two serum markers, CA15 3 and HMFG 2 in localized and metastatic breast cancer.

CA 15 3 is a circulating glycoprotein defined by two monoclonal antibodies (115 D 8 and DF 3) with good specificity for breast cancer. Tumour-associated antigens have been detected by the monoclonal antibody HMFG 2 using a low pH ELISA method. We compare the values obtained using these two assays in patients with localized and metastatic breast cancer. CA 15 3 and HMFG 2 levels were measured in 61 patients, 24 localized and 37 metastatic, evaluated by standard biochemical and radiological testing. Of the patients with metastatic disease 78.4 per cent had an elevated CA 15 3 level whereas only 8.3 per cent of patients with localized disease had an elevated level (chi 2 = 28.2 p = 0.001); 29.8 per cent of patients with metastatic disease had elevated HMFG 2 levels while among those with localized disease 16.7 per cent had elevated levels (chi 2 = 0.57 p = NS). We conclude that only CA 15 3 is a useful marker in advanced disease.

The value of the human milk fat globule membrane antigen HMFG2 in epithelial ovarian cancer monitoring: comparison with CA125.

We assayed serum HMFG2 in serial samples from 215 primary epithelial ovarian cancer patients using an 'in-house' single determinant ELISA, 45% of patients with stage I, 54% with stage II, 61% with stage III and 75% with stage IV disease had elevated serum HMFG2. Post-operative levels were significantly related with residual tumour volume (P < 0.005), and fell in the majority of responders, although the association with response to first-line chemotherapy was not significant. HMFG2 had a sensitivity of 50% specificity of 83%, accuracy of 61%, PVP of 86% and PVN of 45% for disease at second-look laparotomy. Serial levels gave a lead time to clinical relapse in 47% of patients who responded to therapy, including one patient with negative CA125 levels. HMFG, paralleled CA125 in many respects, although it was elevated in fewer patients. In a stepwise discriminant analysis, HMFG2 added to the discrimination of CA125 (r = 0.183, P < 0.005), although additional accurate information was only given in patients with advanced poorly differentiated serous cystadenocarcinoma. Given that HMFG2 is expressed in few patients who are CA125 negative it is unlikely that it will have a significant clinical impact upon patient management.

Measurement of placental alkaline phosphatase activity in benign and malignant pleural effusions.

The usefulness of placental alkaline phosphatase (PLAP) as a diagnostic marker of malignancy was assessed in pleural fluid from 60 patients with effusions. Pleural fluid PLAP activities were measured by an enzyme linked immunoassay (ELISA) using the two monoclonal antibodies H17E2 and H317. Similar values were found in groups of patients with primary bronchial tumours (n = 12), secondary malignancies (n = 23), and "benign" conditions (n = 25). The highest values were found in a small subgroup of patients with metastatic ovarian carcinoma. However, the production of this enzyme by normal lung makes the measurement of PLAP in pleural fluid unhelpful as a diagnostic aid to distinguish "benign" from malignant effusions.

Investigation of the c-neu proto-oncogene related protein, p185, in the serum of primary epithelial ovarian cancer patients.

The relatively high incidence of amplification and overexpression of the neu (c-erb B2/HER-2) oncogene in breast cancer, and its association with poor prognosis, particularly in node negative patients, may allow identification of patients who require aggressive therapy to prevent an early relapse. It's association with ovarian cancer, however, is less well defined than in breast cancer. An ELISA for the c-neu proto-oncogene related protein, p185, has been developed recently using the monoclonal antibodies NB3 and TA1. In the first study of it's kind, we assayed serum samples from patients with primary epithelial ovarian cancer for circulating c-neu p185. Elevated levels were found in 21/178 (11.8%) patients. No correlation was found between serum levels and either the presence or volume of tumor, when assessed either after primary or at second-look surgery. A change in c-neu p185 levels did not correlate with response to chemotherapy. When subjected to univariate and multivariate analyses together with other known prognostic factors, serum c-neu p185 was not a significant predictor of progression-free survival or overall survival. Although c-neu p185 may be involved in the pathogenesis of ovarian cancer, it's assay in serum has no value in prognosis or monitoring.

Serological monitoring of epithelial ovarian cancer.

Serum CA125 measurement has an established role in monitoring epithelial ovarian cancer patients, assisting in determining response to chemotherapy and providing a lead time to clinical relapse. Over the past few years there has been a decrease in the use of second-look laparotomy to determine response; however, this is largely due to the lack of impact that this procedure has on survival rather than the growing use of less invasive scanning techniques or CA 125 assay to determine disease status. The value of a marker lead time depends ultimately on a patient's remaining therapeutic options; the influence on survival of therapeutic intervention at pre-clinical diagnosis of relapse remains to be tested in a randomized controlled trial. The third area where CA 125 may help patient management is in predicting progression-free survival and overall survival. Treating patients with aggressive chemotherapy regimes would not be justified (given the deterioration in the quality of life for a period of months that may result from such therapy) if a poor outcome could be predicted. Deciding when to stop ineffective treatment is extremely difficult for the clinician given patients' desire for active therapy. The prognostic value of CA 125 needs to be further clarified before it can influence such treatment decisions. The aim of this study was to help clarify the role of CA 125 in patient management and to assess several other putative EOC markers, including determinants found on the polymorphic epithelial mucin (PEM)--the most promising alternative marker protein to date.

Immunoassay of CA125 in ovarian cancer: a comparison of three assays for use in diagnosis and monitoring.

There is increasing evidence to support the use of CA125 in the follow-up and management of patients with ovarian cancer and several commercial kits are now available for its measurement. This study investigated and compared the performance of three of them: an enzyme immunoassay (EIA) and an immunoradiometric assay (IRMA) from Abbott Diagnostics, and an IRMA from CIS, U.K. One hundred and thirty-two serum samples from 42 patients with advanced epithelial ovarian cancer were thawed once and assayed for CA125 using each kit. Both IRMAs performed better than the EIA in terms of CV, sensitivity, specificity, and accuracy. The results confirm the usefulness of CA125 as a marker for ovarian cancer. However, discrepancies between results using different kits suggest the need for improved standardization.

Serum placental-like alkaline phosphatase (PLAP): a novel combined enzyme linked immunoassay for monitoring ovarian cancer.

A new combined enzyme linked immunoassay (ELISA) was developed to measure both serum placental-like alkaline phosphatase (PLAP) activity (PLAPA) and concentration (PLAPC) in the same microtitre plate using an Imperial Cancer Research Fund monoclonal antibody, designated H17E2. PLAP A and PLAP C were determined together with an existing marker, CA125 in 397 serial samples from 87 patients with epithelial ovarian cancer. Retrospective assessment showed the sensitivity to increase from 73% with CA125 alone, to 88% using CA125 and PLAP A, and to 93% with all three markers in 261 samples from the patients with known active disease at the time of sampling. When the results for all 397 samples were included in the analysis, however, the specificity, sensitivity, accuracy and predictive powers of this monoclonal antibody were not sufficiently high to assist in the prospective follow up of patients with ovarian cancer. This was due to a significant number of false positive and false negative results. Our data indicate that PLAP A or PLAP C estimation with H17E2 may, therefore, only be of value in the management of those patients with known active disease who are already known to be "marker positive" for this antigen.