 |
|
Patient outcomes linked to biomarker levels by quantitative technology
December 21, 2005New Haven, Conn. - Researchers in the Department of Pathology at Yale University School of Medicine report that when using current pathology methods of biomarker detection, the concentration of antibodies used dramatically alters the apparent relationship of biomarker level to clinical outcome. The paper appears in the December issue of the Journal of the National Cancer Institute
The study, led by David L. Rimm, M.D., associate professor of pathology and member of the Yale Cancer Center, was designed to make sense of inconsistencies in traditional immunohistochemistry, a technique widely used for evaluating biomarker levels. The researchers evaluated levels of the common breast cancer biomarkers HER2, p53 and estrogen receptor (ER) to determine the importance of antibody standardization. They used a tissue microarray format containing specimens from 250 breast cancer patients with available long-term survival data.
"We found that the antibody concentration chosen by pathologists can dramatically affect and even reverse the apparent relationships between biomarker expression levels and patient outcomes," said Rimm. "This work challenges the way pathologists have viewed immunohistochemistry, and points out that biomarker expression studies need further development and analysis."
To standardize measurements, the study used the Automated Quantitative Analysis (AQUATM) technology, a system originally developed to assess biomarker expression in tissue sections. It combined fluorescence-based imaging with automated microscopy and high-throughput tissue microarray analysis technologies.
Their results with AQUATM showed that when a high antibody concentration was used in the assay, low HER2 marker levels were associated with decreased survival. However, if a low antibody concentration was used, high HER2 levels were associated with decreased survival. Results for p53 were similar to those for HER2 but, increased ER levels were associated with increased survival regardless of antibody concentration.
These results suggest that an antibody concentration arbitrarily chosen by the pathologist may not be adequate for the expression range of the biomarker being tested. The apparent reversal of the relationship between marker level and survival rate occurs when there is a non-linear relationship between the antibody concentration and its target. ER was predicted consistently due to a linear relationship.
The findings are of importance as the relationship between protein expression and disease has an increasing role in patient treatments and individualized therapies. Variations in biomarker levels and patient response or outcome have been previously highlighted in the literature, but until now researchers have had no effective method to standardize detection techniques. Creating a new quantitative level of standardization may improve current pathology methods and practices.
"Biomarkers may have the power to provide diagnostic, therapeutic, and prognostic information for personalized medicine." said Donald Earl Henson, M.D., of the George Washington University Cancer Institute, in "Back to the Drawing Board on Immunohistochemistry and Predictive Factors," an accompanying editorial. "However, immunohistochemistry, a popular technique for evaluating biomarker expression, may contain procedural flaws that jeopardize its promise."
Yale University
To standardize measurements, the study used the Automated Quantitative Analysis (AQUATM) technology, a system originally developed to assess biomarker expression in tissue sections. It combined fluorescence-based imaging with automated microscopy and high-throughput tissue microarray analysis technologies.
Their results with AQUATM showed that when a high antibody concentration was used in the assay, low HER2 marker levels were associated with decreased survival. However, if a low antibody concentration was used, high HER2 levels were associated with decreased survival. Results for p53 were similar to those for HER2 but, increased ER levels were associated with increased survival regardless of antibody concentration.
These results suggest that an antibody concentration arbitrarily chosen by the pathologist may not be adequate for the expression range of the biomarker being tested. The apparent reversal of the relationship between marker level and survival rate occurs when there is a non-linear relationship between the antibody concentration and its target. ER was predicted consistently due to a linear relationship.
The findings are of importance as the relationship between protein expression and disease has an increasing role in patient treatments and individualized therapies. Variations in biomarker levels and patient response or outcome have been previously highlighted in the literature, but until now researchers have had no effective method to standardize detection techniques. Creating a new quantitative level of standardization may improve current pathology methods and practices.
"Biomarkers may have the power to provide diagnostic, therapeutic, and prognostic information for personalized medicine." said Donald Earl Henson, M.D., of the George Washington University Cancer Institute, in "Back to the Drawing Board on Immunohistochemistry and Predictive Factors," an accompanying editorial. "However, immunohistochemistry, a popular technique for evaluating biomarker expression, may contain procedural flaws that jeopardize its promise."
Yale University
Biomarker Current Events and Biomarker News RSSCancer metabolism discovery uncovers new role of IDH1 gene mutation in brain cancer
Agios Pharmaceuticals today announced that its scientists have established, for the first time, that the mutated IDH1 gene has a novel enzyme activity consistent with a cancer-causing gene, or oncogene.
Elevated biomarkers lead to diminished quality of life in heart attack patients post-discharge
Many heart attack patients have high levels of cardiac biomarkers in the blood for several months after leaving the hospital, with more shortness of breath and chest pain, according to a Henry Ford Hospital study.
Aileron collaborates study in Nature: Stapled peptides inhibit Notch1 transcription factor
This research validates the potential for Stapled Peptides to modulate key intracellular biological targets, such as transcription factors, that have not been addressable with current small molecule or biologic drug modalities.
Children with autism show slower pupil responses, MU study finds
Autism affects 1 in 150 children today, making it more common than childhood cancer, juvenile diabetes and pediatric AIDS combined.
Hunting for the Prozac Gene
Prozac works wonders for some depressed people, but not for others. In some cases, patients derive little benefit and at worst, it can lead to bizarre hallucinations and fits of rage.
Investment in Parkinson's disease data bank yields potential therapy
Individuals with Parkinson's disease who have higher levels of a metabolite called urate in their blood and in cerebrospinal fluid (CSF) have a slower rate of disease progression.
Use of archived specimens in biomarker studies
Researchers propose a more efficient system using archived specimens for the evaluation of prognostic and predictive biomarkers in a new commentary published online October 8 in the Journal of the National Cancer Institute.
NEDD9 Protein Supports Growth of Aggressive Breast Cancer
Researchers at Fox Chase Cancer Center have demonstrated that a protein called NEDD9 may be required for some of the most aggressive forms of breast cancer to grow. Their findings, based on the study of a mouse model of breast cancer, are presented in a recent issue of Cancer Research, available on-line now.
Study reveals 2/3 of prostate cancer patients do not need treatment
In the largest study of its kind, the international team of pathologists studied an initial 4,000 prostate cancer patients over a period of 15 years to further understanding into the natural progression of the disease and how it should be managed.
New marker for Alzheimer's discovered
Gothenburg researchers have discovered a previously unknown substance in spinal fluid that can be used to diagnose Alzheimer's disease.
More Biomarker Current Events and Biomarker News Articles
 |
Biomarkers of Disease: An Evidence-Based Approach by Andrew K. Trull (Editor), Lawrence M. Demers (Editor), David W. Holt (Editor), Atholl Johnston (Editor), J. Michael Tredger (Editor), Christopher P. Price (Editor) This new publication takes a critical, evidence-based look at the efficacy of new diagnostic tests which are increasingly being used to evaluate organ damage and dysfunction. The use of biomarkers is growing, with a steady stream of new products being brought out by the pharmaceutical industry. However, in many cases the evidence which supports the use of these new methods as opposed to traditional biochemical tests has not yet been demonstrated, and it is intended that this volume will help clarify the strengths and weaknesses of using these biomarkers across a wide range of applications and in the various organs of the body. This approach will provide an invaluable overview of the diverse applications of biomarkers in medicine. |
 |
Disease Markers: Cancer Biomarkers by Sudhir Srivastava (Author), Sudhir Srivastava (Editor) This special book edition of the journal Disease Markers concentrates on molecular biomarkers in cancer research. The main subjects of this book are: Prognostic and predictive markers in cancer; Statistical considerations in combining biomarkers for disease classification; Blood and urine markers for ovarian cancer; Use of markers for the detection and treatment of lung cancer; The promise of biomarkers in colorectal cancer detection; Development tracks for cancer prevention markers; Molecular markers for early detection of cervical neoplasia and Markers of prostate cancer detection, diagnosis and prognosis. This book contains contributions by an international board of experts on the topic. IOS Press is an international science, technical and medical publisher of high-quality books for... |
|
Cancer Biomarkers by Ios Press Original research findings (and reviews solicited by the Editor) on the subject of the identification of markers associated with the disease processes whether or not they are an integral part of the pathological lesion. | |
 |
Biomarker Methods in Drug Discovery and Development (Methods in Pharmacology and Toxicology) by Feng Wang (Editor) Within the pharmaceutical industry, the improvement of drug discovery and development efficiency and the expected personalization of medicine have become vitally important issues. In Biomarker Methods in Drug Discovery and Development, expert researchers provide a tool box for those who have a general interest in biomarker research and for those currently specializing in certain technologies but desiring an understanding of other available methodologies. Its chapters include validated, mature methods as well as new, incredibly promising protocols which aim to apply multiple technologies at different molecular levels in order to surmount the monumental and complex task of transforming the pharmaceutical research and development processes. As a volume in the Methods in Pharmacology and... |
 |
Biomarkers by S.V.S. Rana (Author), Sung-Eun Lee (Author) |
 |
Cardiac Biomarkers in Clinical Practice by James Januzzi (Author) Cardiac Biomarkers in Clinical Practice presents a case based approach to biomarkers in heart diseases including heart failure, ischemic heart disease, and outpatient. Divided into six sections, this book provides physicians and other health care providers with a clear understanding of the role of biomarkers in clinical cardiovascular medicine. |
 |
The Biomarker Guide: Volume 1, Biomarkers and Isotopes in the Environment and Human History (v. 1) by K. E. Peters (Author), C. C. Walters (Author), J. M. Moldowan (Author) Biomarkers are compounds found in crude oil with structures inherited from once-living organisms. They persist in oil spills, refinery products and archaeological artifacts, and can be used to identify the origin, geological age and environmental conditions prevalent during their formation and alteration. These two volumes will be an invaluable resource for geologists, petroleum geochemists, biogeochemists, environmental and forensic scientists, natural product chemists and archaeologists. The first of two volumes of The Biomarker Guide discusses the origins of biomarkers and introduces basic chemical principles relevant to their study. It goes on to discuss analytical techniques, and the applications of biomarkers in environmental and archaeological problems. |
 |
Biomarkers: 10 Determinants of Aging You Can Control by William Evans (Author), Irwin Rosenberg (Author) |
 |
The Biomarker Guide: Volume 2, Biomarkers and Isotopes in Petroleum Systems and Earth History by K. E. Peters (Author), C. C. Walters (Author), J. M. Moldowan (Author) The second volume itemizes parameters used to genetically correlate petroleum and interpret thermal maturity and extent of biodegradation. It documents most known petroleum systems by geologic age throughout Earth history. |
 |
Biomarkers: The 10 Keys to Prolonging Vitality by William Evans (Author) Exciting new evidence from the USDA Human Nutrition Research Center on Aging at Tufts University has demonstrated that the body's decline is due not to the passing of years but to the combined effects of inactivity, poor nutrition, and illness -- much of which can be controlled. This breakthrough study shows that regardless of your age or present physical condition, the aging process can be slowed -- or even reversed! The authors have identified ten "biomarkers," the key physiological factors associated with prolonged youth and vitality: * lean body (muscle) mass |
| © 2009 BrightSurf.com |