Coordinate elevation of serum markers in ovarian cancer but not in benign disease

Abstract

Effective screening for occult ovarian cancer will require a strategy that is both sensitive and specific. Preliminary data suggest that CA 125 is elevated at diagnosis in a majority of patients with ovarian cancer. Although CA 125 is sufficiently specific to prompt its evaluation as one component of a strategy to detect ovarian cancer in postmenopausal women, a further improvement in specificity would facilitate cost‐effective screening. In an attempt to develop a more specific screening strategy, multiple markers were assayed in a panel of sera from 47 patients with ovarian cancer and in a separate panel of sera from 50 individuals with benign disease whose serum CA 125 levels exceeded 35 U/ml. Among the patients with ovarian cancer, elevations of CA 125 (> 35 U/ml) were observed in 91%, CA 15‐3 (> 30 U/ml) in 57%, TAG 72 (> 10 U/ml) in 49%, placental alkaline phosphatase (PLAP) in 25%, human milk fat globule protein (HMFG) 1 in 77%, HMFG2 in 62%, and NB/70K in 57%. Among the 50 sera selected from patients with benign disease, CA 125 was more than 35 U/ml in 100% and more than 65 U/ml in 42%. Among those patients with benign disease and elevated CA 125, NB/70K was elevated in 62%, HMFG1 in 26%, and HMFG2 in 12%, whereas TAG 72 and CA 15‐3 were elevated in only 6% and 2%, respectively. In addition PLAP appeared promising; elevated enzyme levels were not found in the benign disease group. Among patients with ovarian cancer with CA 125 levels more than 35 U/ml, either TAG 72 or CA 15‐3 was elevated in 77%. In the false‐positive group, only 6% had elevations of one or the other marker. The CA 125 levels in cancer patients were, however, substantially greater than in patients with benign disease. If sera from patients with ovarian cancer were diluted to a range comparable to that found in benign disease, at least one of the two confirmatory tests was elevated in 63% of the samples from the malignant cases. Consequently, use of CA 15‐3 and TAG 72 in combination with CA 125 can increase the apparent specificity of the CA 125 assay for distinguishing malignant from benign disease. Prospective studies will be required to test critically whether the use of additional serum markers in combination with the CA 125 assay would contribute to the specificity of a cost‐effective screening strategy for ovarian cancer.

Prevalence screening for ovarian cancer in postmenopausal women by CA 125 measurement and ultrasonography.

“…The expected incidence of ovarian cancer for a population of the same age and sex as the study 16 13 I Serous cystadenocarcinoma 7 13 I Serous cystadenocarcinoma 12 17 I Serous cystadenocarcinoma 14 18 I Clear cell cystadenocarcinoma 9 22…”

“…Firstly, it was not possible to establish whether women with a false negative screening result had ovarian cancer at the time of registration or had developed the disease subsequently. Secondly, it was not possible to establish the 16 13 I Serous cystadenocarcinoma 7 13 I Serous cystadenocarcinoma 12 17 I Serous cystadenocarcinoma 14 18 I Clear cell cystadenocarcinoma 9 22 *This woman declined to return for an ultrasound scan. 100% sensitivity, would require 99-6% specificity to achieve a positive predictive value of 10%.…”

Adjuvant therapy of ovarian cancer with radioactive monoclonal antibody

“…More than 90% of epithelial ovarian tumours express high levels of many antigens (Bast et al, 1991), including one in particular, known as polymorphic epithelial mucin (PEM) (Gendler et al, 1987). PEM can be described as a 'tumour associated antigen' because although expressed extensively by many epithelial cancers it can also be found at low levels on many normal tissues (Arklie et al, 1981).…”

Multiple Biomarker Panels For Early Detection of Ovarian Cancer

“…Examples of these markers include carcinoembryonic antigen, ovarian cystadenocarcinoma antigen, lipid-associated sialic acid, NB/70K, TAG 72.3, CA-15-3 and CA-125. CA-125 is elevated in 82% of women with advanced (stage III or IV) ovarian cancer [10]. However, tumor markers have a limited sensitivity.…”