Cancer Biomarkers - Volume 4, issue 1

Authors: Kerkhof, Marjon | Steyerberg, Ewout W. | Kusters, Johannes G. | van Dekken, Herman | van Vuuren, Adriana J. | Kuipers, Ernst J. | Siersema, Peter D.

Article Type: Research Article

Abstract: Unless detected at an early stage, esophageal adenocarcinoma (EAC) has a poor prognosis. Changes in cellular DNA content and expression levels of p53 and Ki67 in Barrett esophagus (BE) are associated with the development EAC and might serve as markers to identify EAC at an early stage. The aim of this study was to examine the presence of these three markers in various steps of neoplastic progression in BE towards EAC. Dysplasia was graded in 212 biopsy sets taken during follow-up upper endoscopy in 27 patients in whom ultimately high-grade dysplasia (HGD) or EAC was detected. Ploidy status …was determined by flow cytometry, whereas Ki67 and p53 expression were determined by immunohistochemistry. Smoothing splines were used to analyze trends in time. We found an increasing fraction of Ki67 overexpression and, to a lesser extent, abnormal DNA content in biopsies closer to the time-point of detecting HGD/EAC in BE, suggesting the potential value of these biomarkers in identifying patients at increased risk of progression towards HGD/EAC. Accumulation of p53 was seen several years before development of HGD/EAC, and may therefore be an early marker in BE at a stage when dysplasia is not yet detected. A prospective follow-up study is needed to confirm these findings. Show more

Keywords: Barrett esophagus, intestinal metaplasia, p53, Ki67, aneuploidy

DOI: 10.3233/CBM-2008-4101

Citation: Cancer Biomarkers, vol. 4, no. 1, pp. 1-10, 2008

Authors: Troudi, W. | Uhrhammer, N. | Romdhane, K. Ben | Sibille, C. | Amor, M. Ben | El Khil, H. Khodjet | Jalabert, T. | Mahfoudh, W. | Chouchane, L. | Ayed, F. Ben | Bignon, Y.J. | Elgaaied, A. Ben Ammar

Article Type: Research Article

Abstract: Breast cancer, the most commonly diagnosed cancer in women, is the second leading cause of cancer death in women worldwide. To investigate the contribution of BRCA1 gene mutations to familial breast cancer in Tunisia, 32 unrelated patients who had at least one first degree relative affected with breast and/or ovarian cancer were analysed. BRCA1 mutation analysis was performed by DNA sequencing of all BRCA1 exons. We identified four different BRCA1 frameshift mutations: c.4041delAG, c.2551delG and c.5266dupC already been described and one novel mutation, c.211dupA, observed in two unrelated families. C.5266dupC has previously been found among Jewish Ashkenazi and …Eastern European populations. Our study describes it in Arabic/Berber population. Five out of thirty two familial cases had deleterious BRCA1 mutations. Fifteen additional cases carried unclassified variants (UV) or single nucleotide polymorphisms (SNPs). Our study is the first molecular investigation on the role of BRCA1 in hereditary breast cancer in North Tunisia. Show more

Keywords: Family history, breast cancer susceptibility, BRCA1 gene, mutations, UV, SNPs, North Tunisia

DOI: 10.3233/CBM-2008-4102

Citation: Cancer Biomarkers, vol. 4, no. 1, pp. 11-18, 2008

Authors: Block, Timothy M. | Marrero, Jorge | Gish, Robert G. | Sherman, Morris | London, W. Thomas | Srivastava, Sudhir | Wagner, Paul D.

Article Type: Research Article

Abstract: This opinion piece evaluates the degree of readiness of 13 candidate biomarkers or panels of biomarkers for the early detection of hepatocellular carcinoma (HCC), or for the staging of liver fibrosis. As candidate biomarkers for the early detection of disease are identified, it is important to understand where they are in the developmental pipeline and how they might be employed. HCC is a growing public health problem, and its early detection is believed to be important in its management. Current detection methods are limited in usefulness or practicality, and there is a need for better methods to diagnose liver disease. …Therefore, a number of candidate biomarkers, considered to be attractive because of their advanced stage of development or inherent scientific value, were evaluated for specificity and sensitivity for detection of liver disease. Study design, confirmatory evidence and assay practicality associated with each of the biomarkers are considered. The comments in this review reflect the authors' opinions and are based on a recent workshop convened by the Hepatitis B Foundation of America and the US National Cancer Institute's Early Detection Research Network. It is emphasized that only a selected set of biomarkers was considered; thus, this review is not comprehensive and not intended to review all candidate HCC biomarkers. Show more

Keywords: Biomarkers, hepatocellular, carcinoma, fibrosis, cirrhosis

DOI: 10.3233/CBM-2008-4103

Citation: Cancer Biomarkers, vol. 4, no. 1, pp. 19-33, 2008

Authors: Jankovic, Miroslava M. | Milutinovic, Bojana S.

Article Type: Research Article

Abstract: CA125, a coelomic epithelium-related antigen, is expressed in both normal and pathological conditions. In this study, we compared the glycosylation of CA125 antigen from amniotic fluid and the ovarian carcinoma cell line OVCAR-3, in order to detect possible differences as a specific marker of their origin. Antigens from both sources were radiolabelled and subsequently subjected to the affinity chromatography, using plant lectins differing in carbohydrate specificity as ligands. A common chromatographic scheme was applied to all columns, i.e. they were eluted with: a) washing buffer to wash out non-bound and low-affinity bound fractions, b) a solution of inhibitory sugar and …c) a low pH buffer, to release the high affinity bound fractions. CA125 antigen from each source was found to be heterogeneous in respect to the existence of multiple glycoforms, with O-linked glycan chains predominating. However, the binding patterns of both N- and O-linked glycan-reactive lectins indicated distinct differences in carbohydrate composition between CA125 antigen isolated from amniotic fluid and OVCAR-3 cell line. The observed specificites of CA125-oligosaccharide chains might be of special importance from the biomedical aspect, in terms of their possible use for clinical evaluation of gynecological functions in health and disease. Show more

Keywords: Amniotic fluid, CA125, carcinoma cell line, glycoforms, glycosylation, lectin-binding

DOI: 10.3233/CBM-2008-4104

Citation: Cancer Biomarkers, vol. 4, no. 1, pp. 35-42, 2008

Authors: Swellam, Menha | Ragab, Halla M. | Abdalla, Nabila A. | El-Asmar, Abu-Baker H.

Article Type: Research Article

Abstract: Objectives: Determination of tumor biomarkers in serum has been proposed as an alternative and noninvasive way of establishing diagnosis for lung cancer. The aim of this study was to assess the combined use of Cyfra 21-1; the soluble fragment of cytokeratin 19, and soluble E-selectin; endothelial adhesion molecule, for improving the accuracy of diagnosing and screening lung cancer. Materials and methods: Serum Cyfra 21-1 and sE-selectin were determined using electrochemiluminescent immunoassay and enzyme linked immunosorbent assay, respectively, in 52 patients with histologically proven lung cancer, 40 patients with benign lung diseases and 50 healthy volunteers. Results: …Both markers were significantly increased in lung cancer patients as compared to healthy, for benign lung diseases Cyfra 21-1 perform well than sE-selectin. Sensitivities of Cyfra 21-1 and sE-selectin at 95th percentiles of the normal group were 96.2% and 92.3%, while at 95th percentiles of the benign lung diseases were 57.7% and 5%, respectively. In ROC curves, the diagnostic power for the detection of lung cancer was similar for Cyfra 21-1 and sE-selectin; however, when compared with benign lung diseases, Cyfra 21-1 was superior to sE-selectin. The highest sensitivity (99.8%) was reported when the two markers were combined. Conclusion: Cyfra 21-1 and sE-selectin show good performance in detecting lung cancer from normal groups, however, Cyfra 21-1 was superior to sE-selectin in discriminating lung cancer from benign lung diseases. Show more

Keywords: Diagnostic biomarkers, lung cancer, endothelial adhesion molecule, soluble cytokeratin 19 fragment, Cyfra 21-1, soluble E-selectin

DOI: 10.3233/CBM-2008-4105

Citation: Cancer Biomarkers, vol. 4, no. 1, pp. 43-54, 2008