Clinical Utility Of Biomarkers Research Articles

Intestinal metaplasia at the gastroesophageal junction: Barrett's, bacteria, and biomarkers.

For patients found to have intestinal metaplasia at the gastroesophageal junction, technical problems can make it difficult to distinguish short-segment Barrett's esophagus from intestinal metaplasia of the gastric cardia. Whereas the risk of malignancy for the former condition seems to be higher than that for the latter, the distinction between these conditions can have practical clinical implications. Immunostaining for cytokeratins has been proposed as a means to distinguish intestinal metaplasia of esophageal and gastric origins. We review recent data on this issue, and conclude that immunostaining for cytokeratins has no clear advantages over other biomarkers that have been proposed for identifying Barrett's esophagus (e.g., mucin histochemistry, mAb Das-1 immunoreactivity). Presently, the importance of intestinal metaplasia at the gastroesophageal junction remains unclear, and the clinical utility of biomarkers in distinguishing short-segment Barrett's esophagus from intestinal metaplasia of the gastric cardia has not yet been established.

Biomarkers in Cancer Screening: A Public Health Perspective

The last three decades have witnessed a rapid advancement and diffusion of technology in health services. Technological innovations have given health service providers the means to diagnose and treat an increasing number of illnesses, including cancer. In this effort, research on biomarkers for cancer detection and risk assessment has taken a center stage in our effort to reduce cancer deaths. For the first time, scientists have the technologies to decipher and understand these biomarkers and to apply them to earlier cancer detection. By identifying people at high risk of developing cancer, it would be possible to develop intervention efforts on prevention rather than treatment. Once fully developed and validated, then the regular clinical use of biomarkers in early detection and risk assessment will meet nationally recognized health care needs: detection of cancer at its earliest stage. The dramatic rise in health care costs in the past three decades is partly related to the proliferation of new technologies. More recent analysis indicates that technological change, such as new procedures, products and capabilities, is the primary explanation of the historical increase in expenditure. Biomarkers are the new entrants in this competing environment. Biomarkers are considered as a competing, halfway or add-on technology. Technology such as laboratory tests of biomarkers will cost less compared with computed tomography (CT) scans and other radiographs. However, biomarkers for earlier detection and risk assessment have not achieved the level of confidence required for clinical applications. This paper discusses some issues related to biomarker development, validation and quality assurance. Some data on the trends of diagnostic technologies, proteomics and genomics are presented and discussed in terms of the market share. Eventually, the use of biomarkers in health care could reduce cost by providing noninvasive, sensitive and reliable assays at a fraction of the cost of definitive technology, such as CT scan. The National Cancer Institute's Early Detection Research Network (EDRN) has begun an innovative, investigator-initiated project to improve methods for detecting the biomarkers of cancer cells. The EDRN is a consortium of more than 32 institutions to link discovery of biomarkers to the next steps in the process of developing early detection tests. These discoveries will lead to early clinical validation of tests with improved accuracy and reliability.

Gene expression in papillary thyroid carcinoma reveals highly consistent profiles.

Papillary thyroid carcinoma (PTC) is clinically heterogeneous. Apart from an association with ionizing radiation, the etiology and molecular biology of PTC is poorly understood. We used oligo-based DNA arrays to study the expression profiles of eight matched pairs of normal thyroid and PTC tissues. Additional PTC tumors and other tissues were studied by reverse transcriptase-PCR and immunohistochemistry. The PTCs showed concordant expression of many genes and distinct clustered profiles. Genes with increased expression in PTC included many encoding adhesion and extracellular matrix proteins. Expression was increased in 8/8 tumors for 24 genes and in 7/8 tumors for 22 genes. Among these genes were several previously known to be overexpressed in PTC, such as MET, LGALS3, KRT19, DPP4, MDK, TIMP1, and FN1. The numerous additional genes include CITED1, CHI3L1, ODZ1, N33, SFTPB, and SCEL. Reverse transcriptase-PCR showed high expression of CITED1, CHI3L1, ODZ1, and SCEL in 6/6 additional PTCs. Immunohistochemical analysis detected CITED1 and SFTPB in 49/52 and 39/52 PTCs, respectively, but not in follicular thyroid carcinoma and normal thyroid tissue. Genes underexpressed in PTC included tumor suppressors, thyroid function-related proteins, and fatty acid binding proteins. Expression was decreased in 7/8 tumors for eight genes and decreased in 6/8 tumors for 19 genes. We conclude that, despite its clinical heterogeneity, PTC is characterized by consistent and specific molecular changes. These findings reveal clues to the molecular pathways involved in PTC and may provide biomarkers for clinical use.