Mammary Carcinoma and Tumor Markers – State of the Art

Mammary Carcinoma and Tumor Markers – State of the Art

The third symposium, organised by the Tumormarkers Work Group, was devoted to mammary carcinoma. The strategy of the earlier symposia was applied again: clinical presentations in the morning and support by the laboratory for the diagnostic proceedings and follow-up in the afternoon. First, the epidemiology was discussed, including risk factors, early detection and screening. Integration of the anatomical pathology, where the vessel structures are scored, with the measurement of a tumormarker with low (TPS) or high (CA 15-3) molecular weight may provide better understanding of the release of the markers. Nowadays, early detection results in more cases of pre-invasive ductal carcinoma in situ (DCIS) and demands a different surgical regime. The morning session was closed with the adjuvant therapy for metastatic carcinoma. High doses of cytostatics are combined with bone marrow replacement or peripheral stem cell transplantation. Despite promising results in a selected high-risk population, this approach should be applied only in the setting of clinical studies, because of morbidity and costs. The role of episialin (CA 15-3) in the adhesion of tumor cells was elucidated in the afternoon, and currently certain patterns of episialin expression on primary mammary carcinoma can be found that correlate with metastasis to the axillary lymph nodes. Measurement of serum levels of tumormarkers has no value for screening or detection, but is useful during follow-up and monitoring of the patient. The many different assays with monoclonals against different epitopes of episialin were reviewed, which is important for understanding the discrepancies in results obtained with these diagnostic products. The diagnostic and prognostic tools of molecular biological origin enable us to define patient groups who are in need of specific therapeutic intervention. The DNA amplification technique has to be integrated in the laboratories for clinical chemistry as soon as possible. More than a hundred participants took part in the lively discussions and made a fruitful contribution to this symposium which was sponsored by BykNetherlands.
VEGF, MMP-9 and TIMP-I in Dx for Breast Cancer

VEGF, MMP-9 and TIMP-I in Dx for Breast Cancer

Vascular endothelial growth factor (VEGF), matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 may play a role in the pathogenesis of cancer disease. We investigated their levels and utility in comparison to cancer antigen (CA) 15-3 in patients with breast cancer (BC) and in relation to the control groups. The study included 100 women with BC, 50 patients with benign breast tumor, and 50 healthy women. The plasma levels of the tested parameters were determined using enzyme-linked immunosorbent assay, while CA 15-3 with chemiluminescent microparticle immunoassay. The results demonstrated significant differences in the concentration of the tested parameters and CA 15-3 between groups of patients with BC and healthy patients or patients with benign breast tumor. The plasma levels of VEGF and tissue inhibitor of metalloproteinase-1 were significantly higher in advanced tumor stages. The tested parameters were comparable to CA 15-3 values of the diagnostic sensitivity, specificity, the predictive values of positive and negative test results, and the area under the receiver-operating characteristic curve. The combined use of the tested parameters with CA 15-3 resulted in the increase in sensitivity, negative predictive value, and area under the receiver-operating characteristic curve, especially in the combination of VEGF with tumor marker (84%, 73%, 0.888, respectively). These findings suggest the usefulness of the tested parameters in the diagnosis of BC. VEGF, especially in combination with CA 15-3, showed the highest usefulness in the diagnosis of early BC.
CEA, MCA, CA 15.3 and CA 549 in Breast Cancer

CEA, MCA, CA 15.3 and CA 549 in Breast Cancer

Serum levels of carcinoembryonic antigen (CEA), mucin-like carcinoma-associated antigen (MCA), CA 15.3 and CA 549 were concurreutly assayed in patients with metastatic breast cancer. Overall sensitivity in detecting metastatic breast cancer (201 pts) was CEA 45%, MCA 59%, CA 15.3 71% and CA 549 72% (P < 0.01). Sensitivity increased by only 6% to 8% when two or more antigens were simultaneously considered. An overall sensitivity of correlation with objective response (n = 71) was observed in the range of 53-67% (P = n.s.) in patients with abnormal baseline marker values, and in the range of 4287% (P < 0.05) in patients with normal baseline values. The combination of two or more markers did not improve sensitivity, but decreased specificity of correlation with objective response. In conclusion, CA 15.3 and CA 549 have individually higher sensitivity in detecting metastatic breast cancer. No clinical advantage was observed for using two or more markers concurrently over CA 15.3 or CA 549 alone in the monitoring of metastatic breast cancer.
8-hydroxy-2-deoxyguanosine (8-OHdG) as a critical biomarker of oxidative stress and carcinogenesis

8-hydroxy-2-deoxyguanosine (8-OHdG) as a critical biomarker of oxidative stress and carcinogenesis

There is extensive experimental evidence that oxidative damage permanently occurs to lipids of cellular membranes, proteins, and DNA. In nuclear and mitochondrial DNA, 8-hydroxy-2 -deoxyguanosine (8-OHdG) or 8-oxo-7,8-dihydro-2 -deoxyguanosine (8-oxodG) is one of the predominant forms of free radical-induced oxidative lesions, and has therefore been widely used as a biomarker for oxidative stress and carcinogenesis. Studies showed that urinary 8-OHdG is a good biomarker for risk assessment of various cancers and degenerative diseases. The most widely used method of quantitative analysis is high-performance liquid chromatography (HPLC) with electrochemical detection (EC), gas chromatography-mass spectrometry (GC-MS), and HPLC tandem mass spectrometry. In order to resolve the methodological problems encountered in measuring quantitatively 8-OHdG, the European Standards Committee for Oxidative DNA Damage was set up in 1997 to resolve the artifactual oxidation problems during the procedures of isolation and purification of oxidative DNA products. The biomarker 8-OHdG or 8-oxodG has been a pivotal marker for measuring the effect of endogenous oxidative damage to DNA and as a factor of initiation and promotion of carcinogenesis. The biomarker has been used to estimate the DNA damage in humans after exposure to cancer-causing agents, such as tobacco smoke, asbestos fibers, heavy metals, and polycyclic aromatic hydrocarbons. In recent years, 8-OHdG has been used widely in many studies not only as a biomarker for the measurement of endogenous oxidative DNA damage but also as a risk factor for many diseases including cancer.
a href="https://gnosis.bioprognos.com/wp-content/uploads/20090311-8-hydroxy-2-deoxyguanosine8-OHdG-as-a-critical-biomarker-of-oxidative-stress-and-carcinogenesis.pdf" target="_blank">
CA M26 and CA M29 in Breast Cancer

CA M26 and CA M29 in Breast Cancer

Two recently developed monoclonal antibody (MAbkbased anti-mucin assays, CA M26 and CA M29, were studied in 250 cancer patients and compared to 3 well-established marker tests, viz., CA 125, CA 15.3 and SCC, in order to assess their clinical usefulness as serum tumor markers. Pre-treatment sera were obtained from patients with predominantly lowstage epithelial malignancies comprising 200 adenocarcinomas (of the ovary, endometrium, breast and large intestine) and 50 squamous-cell carcinomas (of the uterine cervix). Pretreatment sera of 50 patients with benign ovarian tumors were included to evaluate levels in benign disease. CA M26 and CA M29 cut-off levels were established in 89 healthy controls. In patients with adenocarcinomas, overall positivity for CA M29 was 2476, ranging from 10% in breast cancer to 60% in ovarian cancer. Overall positivity was highest for CA 125 (30%) and lowest for CA M26 (I 8%) with CA M29 (24%) being similar to CA 15.3 (25%). In adenocarcinomas the combined CA M26-CA M29 assays equalled results obtained with the CA 125-CA 15.3 combination (33% vs. 36%). Elevation of 2 or more markers was highly indicative of advanced disease (p < 0.025). A majority of positive patients showed either CA M26 or CA M29 elevations, indicating that both antibodies detect distinct epitopes. After adjustment for tumor site and stage, the profile of CA M26 as a single marker differed significantly from the profiles of CA 125 and of CA M29. CA M26 was frequently (32%) elevated in patients with squamous-cell carcinoma of the cervix and CA M26 levels were often independently elevated. CA M26 seems to be valuable as an additional marker in breast cancer and perhaps as a new marker in cervical cancer. CA M29 may be useful in ovarian cancer in addition to CA 125.
Association of plasma NGAL with sepsis and acute kidney dysfunction

Association of plasma NGAL with sepsis and acute kidney dysfunction

Neutrophil gelatinase-associated lipocalin (NGAL) is secreted by injured kidney cells as well as by activated neutrophils in response to bacterial infections. We assessed the influence of acute renal dysfunction on the association between plasma NGAL and sepsis. NGAL was measured daily in 138 critically ill patients. Simultaneous recordings of sepsis status and fluctuations in renal function were made. Elevated NGAL was associated with sepsis independent of level of acute renal dysfunction. A cut-off value of 98 ng/mL distinguished sepsis from systemic inflammation with high sensitivity (0.77) and specificity (0.79). Plasma NGAL can help clinicians to identify bacterial infections in critically ill patients.
Clinical significance of serum EGFR levels in patients with Breast Cancer

Clinical significance of serum EGFR levels in patients with Breast Cancer

Epidermal growth factor receptor (EGFR) plays an important role in the pathogenesis of multiple malignancies and its expression strongly also affects the outcomes of cancer patients. The objective of this study was to determine the clinical significance of the serum levels of EGFR in breast cancer (BC) patients. A total of 96 patients with a pathologically confirmed diagnosis of BC were enrolled into this study. Serum EGFR levels were determined by the solid-phase sandwich ELISA method. Age and sex matched 30 healthy controls were included in the analysis. Median age of diagnosis was 48 years old (range: 29–80). Thirty-seven (39%) consisted of metastatic disease. The baseline serum EGFR levels were significantly higher than in the healthy control group (p < 0.001). The serum EGFR concentrations were also significantly higher only in patients with ER-negative and triple-negative tumor (p = 0.05 and p = 0.04, respectively). The other known clinical variables, including grade of histology, stage of disease, serum CA 15.3 levels, and response to chemotherapy were not found to be correlated with serum EGFR concentrations (p > 0.05). Likewise, serum EGFR levels were found to play no prognostic role for survival (p = 0.35). In conclusion, while serum EGFR levels were elevated in BC patients, EGFR level has no predictive and prognostic value in these patients.
Analysis of blood markers for early Breast Cancer diagnosis

Analysis of blood markers for early Breast Cancer diagnosis

Breast cancer is the most common neoplasm in women and has the highest associated mortality rate. Rapid detection programmes can provide early diagnosis and increase the chances of survival. There are no specific tumor biomarkers for the early phase of the disease. The primary aim of this study was to search a blood biomarker with levels that exceeded the normal range established in the general population that could be used to screen breast cancer.Case–control study. Conventional as well as research (NGAL, EGFR and 8-OHdG) tumor biomarkers were analyzed.
Clinical use of biomarkers in Breast Cancer – Updated Guidelines from the European Group on Tumor Marker (EGTM)

Clinical use of biomarkers in Breast Cancer – Updated Guidelines from the European Group on Tumor Marker (EGTM)

Biomarkers play an essential role in the management of patients with invasive breast cancer. For selecting patients likely to respond to endocrine therapy, both oestrogen receptors (ERs) and progesterone receptors (PRs) should be measured on all newly diagnosed invasive breast cancers. On the other hand, for selecting likely response to all forms of antiHER2 therapy (trastuzumab, pertuzumab, lapatinib or ado-trastuzumab emtansine), determination of HER2 expression or gene copy number is mandatory. Where feasible, measurement of ER, PR and HER2 should be performed on recurrent lesions and the primary invasive tumour. Although methodological problems exist in the determination of Ki67, because of its clearly established clinical value, wide availability and low costs relative to the available multianalyte signatures, Ki67 may be used for determining prognosis, especially if values are low or high. In oestrogen receptor (ER)-positive, HER2-negative, lymph nodeenegative patients, multianalyte tests such as urokinase plasminogen activator (uPA)-PAI-1, Oncotype DX, MammaPrint, EndoPredict, Breast Cancer Index (BCI) and Prosigna (PAM50) may be used to predict outcome and aid adjunct therapy decision-making. Oncotype DX, MammaPrint, EndoPredict and Prosigna may be similarly used in patients with 1e3 metastatic lymph nodes.
M-CSF, MMP-9 and TIMP-I Dx Biomarkers for Breast Cancer

M-CSF, MMP-9 and TIMP-I Dx Biomarkers for Breast Cancer

Macrophage colony­stimulating factor (M­CSF), matrix metalloproteinase­9 (MMP­9), and its specific tissue inhibitor ­ tissue inhibitor of metalloproteinases­1 (TIMP­1) may play an important role in the pathogenesis and spread of cancer. We investigated the plasma levels of M­CSF, MMP­9, and TIMP­1 in comparison with a commonly accepted tumor marker CA 15­3 in breast cancer patients and in control groups. The cohort included 110 breast cancer patients in groups at stages I­IV. The control group consisted of 50 healthy volunteers and 50 benign tumor patients. Plasma levels of M­CSF, MMP­9, and TIMP­1 were determined by using ELISA, while CA 15­3 concentrations were determined by using chemiluminescent microparticle immunoassay (CMIA).