New tumor markers: CA125 and beyond

University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
International Journal of Gynecological Cancer (Impact Factor: 1.96). 10/2005; 15 Suppl 3(Suppl 3):274-81. DOI: 10.1111/j.1525-1438.2005.00441.x
Source: PubMed


A variety of biomarkers have been developed to monitor growth of ovarian cancer and to detect disease at an early interval. CA125 (MUC16) has provided a useful serum tumor marker for monitoring response to chemotherapy, detecting disease recurrence, distinguishing malignant from benign pelvic masses, and potentially improving clinical trial design. A rapid fall in CA125 during chemotherapy predicts a favorable prognosis and could be used to redistribute patients on multiarmed randomized clinical trials. Several studies now document that CA125 can serve as a surrogate marker for response in phase II trials. Serial measurement of CA125 might also provide a useful marker for monitoring stabilization of disease with cytostatic targeted therapeutic agents. The greatest potential for serum markers may be in detecting ovarian cancer at an early stage. A rising CA125 can be used to trigger transvaginal sonography (TVS) in a small fraction of patients. An algorithm has been developed that calculates risk of ovarian cancer based on serial CA125 values and refers patients at highest risk for TVS. Use of the algorithm is currently being evaluated in a trial with 200,000 women in the UK that will test critically the ability of a two-stage screening strategy to improve survival in ovarian cancer. Whatever the outcome, as 20% of ovarian cancers have little or no expression of CA125, additional serum markers will be required to detect all patients in an initial phase of screening. More than 30 serum markers have been evaluated alone and in combination with CA125 by different investigators. Some of the most promising include: HE4, mesothelin, M-CSF, osteopontin, kallikrein(s), and soluble EGF receptor. Two proteomic approaches have been used: one examines the pattern of peaks on mass spectroscopy and the other uses proteomic analysis to identify a limited number of critical markers that can be assayed by more conventional methods. Both approaches are promising and require further development. Several groups are placing markers on multiplex platforms to permit simultaneous assay of multiple markers with very small volumes of serum. Mathematical techniques are being developed to analyze combinations of marker levels to improve sensitivity and specificity. In the future, serum markers should improve the sensitivity of detecting recurrent disease as well as facilitate earlier detection of ovarian cancer.

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    • "11522.6, and 11537.7 Dalton. So far, more than 30 serum markers have been evaluated alone or in combination with CA125, for example, lysophosphatidic acid, osteopontin, ovarian carcinoma associated antigen, and HE4 for testing their qualifications as biomarkers [10, 11]. One recent study reported higher specificity and sensitivity for early detection of ovarian cancer by using a combination of 4 markers (APAO1, a truncated form of transthyretin, a fragment of inter-α-trypsin inhibitor heavy chain H4, and CA125) compared to conventional marker CA125 alone [7]. "
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    ABSTRACT: A combination of peptide ligand library beads (PLLB) and 1D gel liquid chromatography-mass spectrometry/mass spectrometry (1DGel-LC-MS/MS) was employed to analyze serum samples from patients with ovarian cancer and from healthy controls. Proteomic analysis identified 1200 serum proteins, among which 57 proteins were upregulated and 10 were downregulated in the sera from cancer patients. Retinol binding protein 4 (RBP4) is highly upregulated in the ovarian cancer serum samples. ELISA was employed to measure plasma concentrations of RBP4 in 80 samples from ovarian cancer patients, healthy individuals, myoma patients, and patients with benign ovarian tumor, respectively. The plasma concentrations of RBP4 ranging from 76.91 to 120.08 ng/mL with the mean value 89.13 ± 1.67 ng/mL in ovarian cancer patients are significantly higher than those in healthy individuals (10.85 ± 2.38 ng/mL). Results were further confirmed with immunohistochemistry, demonstrating that RBP4 expression levels in normal ovarian tissue were lower than those in ovarian cancer tissues. Our results suggested that RBP4 is a potential biomarker for diagnostic of screening ovarian cancer.
    BioMed Research International 08/2014; 2014:179040. DOI:10.1155/2014/179040 · 2.71 Impact Factor
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    • "Today, the most commonly used combination is that in which CA-125 and imaging methods are used together (Ashrafgangooei and Rezaeezadeh, 2011). However, this combination is not sufficient for early diagnosis due to the low sensitivity of CA-125 and the cost of imaging methods (Bast et al., 2005). Therefore, development a new marker to increase the early detection rate is necessary. "
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    ABSTRACT: Background: The present study aimed to investigate the utility and importance of the various parameters of complete blood count panel for benign-malignant differentiation of adnexal masses. Materials and methods: This retrospective study involved 316 patients with documented benign and 253 patients with malignant adnexal masses who underwent primary surgical treatment at a tertiary referral center. Prior to the study, all benign and malignant cases were compared within their own groups and then the benign and malignant cases were compared to each other. For all cases, cut-off, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for the neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), neutrophil, lymphocyte, platelet and CA-125 parameters, and the results were compared in regards to the groups. Results: NLR, PLR, neutrophil, CA-125, and platelet values were higher in the malignant compared to the benign cases (p<0.01). The lymphocyte value was lower in the malignant cases (p<0.01). No significant differences were found for basophils and eosinophils (p > 0.05). For CA-125, the sensitivity, specificity, PPV and NPV for all cases were 78%, 62%, 62% and 78%, respectively. For NLR, they were 65.6%, 72.1%, 65.3%, and 72.3%, and for PLR, 48%, 81%, 67%, and 66%. Additionally, the sensitivity and specificity were 55% and 77% for CA-125, 66% and 58% for NLR, and 61% and 58% for PLR in early malignant cases. Conclusions: NLR and PLR appear to be useful methods that can be applied together with CA-125 due to the relatively high sensitivity values for the malign-benign differentiation of ovarian masses. Although the specificity of these parameters is lower than CA-125, especially in cases with early malignant ovarian pathology, their sensitivity being higher is promising for the early diagnosis of ovarian cancer. It can be used to detect ovarian malignancies in the early stages, and it will increase the treatment options and improve survival rates.
    Asian Pacific journal of cancer prevention: APJCP 08/2014; 15(16):6881-5. DOI:10.7314/APJCP.2014.15.16.6881 · 2.51 Impact Factor
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    • "To date, the cancer antigen 125 (CA125) is the most commonly used tumor marker in the evaluation and clinical management of an ovarian mass, but since it has a low specificity, especially in premenopausal women [13,14], the search for complementary biomarkers is pivotal. Human Epididymis Protein 4 (HE4), a whey-acid protein first isolated in the epithelium of human epididymis and in epithelial cells of the respiratory system as well as in the female reproductive tract [15-17], offers superior specificity in the differentiation of benign and malignant adnexal masses in premenopausal women compared to CA125 [18]. "
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    ABSTRACT: Borderline tumors of the ovary (BOT) are a distinct entity of ovarian tumors, characterized by lack of stromal invasion. Recent studies postulated that the presence of invasive implants, incomplete staging, fertility sparing surgery and residual tumor after surgery are major prognostic factors for BOT. There are no biomarkers that can predict BOT or the presence of invasive implants. The aim of our study was to assess the value of CA125 and HE4 alone, or within ROMA score for detecting BOT, and for predicting the presence of invasive implants. Retrospective, monocentric study on 167 women diagnosed with BOT or benign ovarian masses. Serum HE4, CA125 levels and ROMA were assessed preoperatively. Due to low number of BOT with invasive implants, we performed an unmatched analysis (consecutive patients) and a matched analysis (according to age and histology) to compare BOT with invasive implants, BOT without invasive implants and benign disease. There were no significant differences in the HE4 and CA125 expressions in the three groups of patients (p = 0.984 and p = 0.141, respectively). The ROC analysis showed that CA125 alone is superior to ROMA and HE4 in discriminating patients with BOT with invasive implants from patients with benign diseases and BOT without invasive implants. A newly established score, ROMABOT, did not perform better than ROMA. The analysis of the matched groups revealed similar results as the analysis of all samples. Both HE4 and CA125 are not reliable biomarkers for the diagnosis of BOT or for predicting the presence of invasive implants.
    Journal of Ovarian Research 05/2014; 7(1):49. DOI:10.1186/1757-2215-7-49 · 2.43 Impact Factor
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