Cancer Biomarkers - Volume 1, issue 4-5

Authors: Barker, Peter E.

Article Type: Editorial

DOI: 10.3233/CBM-2005-14-501

Citation: Cancer Biomarkers, vol. 1, no. 4-5, pp. 207-208, 2005

Authors: Michaud, Ginette Y.

Article Type: Research Article

Abstract: In the field of clinical laboratory medicine, standardization is aimed at increasing the trueness and reliability of measured values. Standardization relies on the use of written standards, reference measurement procedures and reference materials. These are important tools for the design and validation of new tests, and for establishing the metrological traceability of diagnostic assays. Their use supports the translation of research technologies into new diagnostic assays and leads to more rapid advances in science and medicine, as well as improvements in the quality of patient care. The various standardization tools are described, as are the procedures by which written standards, …reference procedures and reference materials are developed. Recent efforts to develop standards for use in the field of molecular diagnostics are discussed. The recognition of standardization tools by the FDA and other regulatory authorities is noted as evidence of their important role in ensuring the safety and performance of in vitro diagnostic devices. Show more

Keywords: Written standards, reference measurement procedures, reference materials, metrological traceability, Food and Drug Administration

DOI: 10.3233/CBM-2005-14-502

Citation: Cancer Biomarkers, vol. 1, no. 4-5, pp. 209-216, 2005

Authors: Winn-Deen, Emily S.

Article Type: Research Article

Abstract: The majority of genetic tests done today are completely home brew assays. A few of the more common tests are based on ASR level reagents. To date the only genetic assays that are available as FDA-approved in vitro diagnostic (IVD) kits are for analysis of the Factor V (Leiden) and Factor II (promoter G to A) mutations associated with thrombophilia risk for assessment of cytochrome P450 2D6 and 2C19 polymorphisms and for analysis of mutations in the CFTR gene. In this regard, the lab community has taken the lead in development of standards and controls for genetic tests. As genetic …testing enters the mainstream, we expect to see more approvals of IVD kits, and the IVD manufacturing community will take a larger role in providing the control materials for these assays. Commercially run proficiency testing programs are only available for the most common genetic tests. All other tests must use approaches such as sample swapping between labs to fulfill this requirement. Show more

DOI: 10.3233/CBM-2005-14-503

Citation: Cancer Biomarkers, vol. 1, no. 4-5, pp. 217-220, 2005

Authors: Amos, Michael D. | Bridges, Alan J.

Article Type: Research Article

Abstract: It is widely held that determination of increased levels of serum autoantibodies can play an important role in the diagnosis and, in some cases, management of many autoimmune diseases. It is also widely held that such testing is fraught with problems relating to accuracy and detection of clinically relevant autoantibodies. Attempts to standardize autoantibody testing by making available standard reference sera, have helped to some degree to improve the testing. Nevertheless, problems still exist and may be causing the delayed diagnosis of severely debilitating and sometimes fatal autoimmune diseases. This paper discusses current practice, as well as, possible new approaches …intended to make more robust, autoantibody determinations in all fields of medicine. Show more

DOI: 10.3233/CBM-2005-14-504

Citation: Cancer Biomarkers, vol. 1, no. 4-5, pp. 221-227, 2005

Authors: Rhodes, Anthony

Article Type: Research Article

Abstract: Advancements in medical genetics are resulting in the identification of key molecules in the pathways that lead to carcinogenesis. With these discoveries, drugs are developed that target a protein or block a particular molecular pathway with the potential to bring about disease regression. The HER2/neu tyrosine kinase receptor is one such target. Therapy based on the humanised monoclonal antibody, trastuzumab, targets HER-2/neu and inhibits the growth of HER2/neu-overexpressing breast cancer cells. Assays for markers to HER2/neu are forerunners of many more predictive assays that are likely to enter the clinical arena in the near future, many of which will require …quantitative analysis. In the field of tissue based assay systems controversies are well documented on the lack of reproducibility in the immunohistochemical analysis HER2/neu. The problems encountered to date lye with the difficulty in reliably standardising the immunohistochemical assay. One of the first steps in addressing this issue is to develop a standard reference material against which the 'variable' of assay sensitivity for HER2/neu can be accurately gauged. Work in the United States and Europe aimed at providing a standard reference material for HER2/neu has already commenced. Preliminary work conducted in Europe shows that development of a standard comprised of cell lines is feasible and when employed as part of an external quality assurance programme, results in significant improvement in the numbers of clinical laboratories achieving appropriate results. In the United States it has been proposed that two standards consisting of well characterized cell lines will be produced, one a National Institute of Standards and Technology (NIST) – certifiable standard, and the other a commercially developed standard for use in all HER2/neu testing. The aim is that this approach will act as a template for other important predictive markers of the future. Show more

Keywords: Predictive assays, HER2/neu, immunohistochemistry, cell lines, standard reference materials

DOI: 10.3233/CBM-2005-14-505

Citation: Cancer Biomarkers, vol. 1, no. 4-5, pp. 229-232, 2005

Authors: O'Connell, Catherine D. | Atha and, Donald H. | Jakupciak, John P.

Article Type: Research Article

Abstract: As large scale genomics and proteomics efforts identify an increasingly complex list of biomarkers to identify human disease, populations predictive for that disease, and drug or other therapy responses for treatment, attention is needed in the research and development arena to bring initial discoveries to clinical utility. This article reviews the process of biomarker test verification and analytical validation, utilizing measurement standardization. Two such measurement programs are described in this manuscript: the identification of mutations in human mitochondrial DNA, and the measurement of telomerase activity in cancer. These model programs address the need for a standardized procedure outlining critical steps …to assessing whether a biomarker assay should proceed to clinical validation, and to identify whether reference materials development is needed to establish measurement accuracy and sensitivity. Show more

Keywords: Mitochondria, telomerase, diagnostics, traceable controls

DOI: 10.3233/CBM-2005-14-506

Citation: Cancer Biomarkers, vol. 1, no. 4-5, pp. 233-239, 2005

Authors: Chatla, Chakrapani | Jhala, Nirag C. | Katkoori, Venkat R. | Alexander, Dominik | Meleth, Sreelatha | Grizzle, William E. | Manne, Upender

Article Type: Research Article

Abstract: Although decreased or lack of expression of Bcl-2 has been correlated with advanced tumor stage and shortened patient survival in colorectal cancer (CRC), its value in predicting the recurrence has not been well explored. Therefore, we assessed the usefulness of phenotypic expression of Bcl-2 in non-Hispanic Caucasian patients with CRCs in identifying risk of recurrence. Archival tissues of 92 Stage II and 66 Stage III primary CRCs were evaluated for immunohistochemical expression of Bcl-2. None of these patients received either pre- or post-surgical adjuvant therapies. Kaplan-Meier and Cox proportional hazards methods were used to estimate the rates of recurrence and …survival according to Bcl-2 expression. Decreased expression of Bcl-2 was associated with an increased rate of recurrence in patients with Stage II CRCs (5-year log-rank test P=0.0015; Hazard Ratio (HR)=3.90, 95%C.I.:1.55–9.77) but not with Stage III CRCs (5-year log-rank test P=0.6058; HR=1.07, 95%C.I.:0.47–2.45) after adjusting for other demographic and clinicopathological features. Furthermore, decreased expression of Bcl-2 was an indicator of short survival in patients with Stage II CRCs but not with Stage III CRCs. Thus, decreased or lack of Bcl-2 expression in primary CRCs may serve as a molecular biomarker of high risk of recurrence for Caucasian patients with Stage II CRCs. These findings might be useful in identifying biologically aggressive phenotypes of Stage II CRCs, and may aid the oncologist in designing maximally appropriate therapeutic regimens. Show more

Keywords: Colorectal adenocarcinoma, Bcl-2 expression, tumor stage, caucasians, recurrence, and prognosis

DOI: 10.3233/CBM-2005-14-507

Citation: Cancer Biomarkers, vol. 1, no. 4-5, pp. 241-250, 2005

Authors: Vijayalakshmi, K. | Vettriselvi, V. | Krishnan, M. | Shroff, Sunil | Jayanth, Vikram R. | Paul, Solomon F.D.

Article Type: Research Article

Abstract: CYP1A1 activates environmental procarcinogens and catalyzes oxidative metabolism of estrogens and is likely to play an important role in the etiology of prostate cancer. To evaluate this phenomenon, the association between two single nucleotide polymorphisms (A to G transition in exon7 leading to amino acid substitution Ile462Val and T3801C at 3'UTR) of CYP1A1 gene in prostate cancer were analyzed in a case-control study of 100 individuals in South Indian population. The estimated relative risk was significantly high for individuals with w1/m1 genotype at 3'UTR of CYP1A1 gene (OR-4.64; 95%CI = 1.51–14.86; P ‹ 0.01) whereas the CYP1A1 Ile/Val genotype (w2/m2) …on exon 7 was found to be associated with a decreased risk for prostate cancer (OR-0.17; 95%CI = 0.02–0.89; P=0.03). A Stratified analysis of the genotypes with age of onset and tumor grade showed the w1/m1 genotype to be significantly associated with an early age of onset; however the tumor grades did not have significant association with the variant genotypes. Thus the present study indicates that individuals with the variant w1/m1 genotype exhibit an increased risk while those with w2/m2 genotype exhibit a decreased risk for prostate cancer. Show more

Keywords: CytochromeP4501A1, 3'UTR, polymorphisms, prostate cancer

DOI: 10.3233/CBM-2005-14-508

Citation: Cancer Biomarkers, vol. 1, no. 4-5, pp. 251-258, 2005