Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Patient outcomes linked to biomarker levels by quantitative technology

22.12.2005


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.


A multiplex image analyzed by AQUA to quantitatively analyze protein expression. Different colors represent compartments where protein concentration is measured; the number of pixels of each color is compared to the total number of pixels to give protein concentration.



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 (AQUA™) 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 AQUA™ 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.”

In follow up to the editorial, Dennis C. Sgroi, M.D., director of Breast Pathology at the Massachusetts General Hospital and an associate professor of Pathology at the Harvard Medical School noted, “AQUA has proven to be a very effective tool in determining the flaws and inconsistencies associated with immunohistochemistry. These findings warrant review by pathologists in questioning the validity of current practices and before the data from predictive biomarker studies is formally integrated into practice and patient treatment.”

Co-authors at Yale include Anthony McCabe, Marisa Dolled-Filhart, Robert L. Camp. The study was funded by grants from The Department of Defense Breast Cancer Research Program, the National Cancer Institute of the National Institutes of Health, the Greenwich Breast Cancer Alliance, and the Patrick and Catherine Weldon Donaghue Foundation for Medical Research.

Camp and Rimm are founders, stockholders, and consultants to HistoRx, a private corporation to which Yale University has given exclusive rights to produce and distribute the software and technologies embedded in AQUA™. For further information contact Robert A. Curtis, bcurtis@historx.com, or 203-498-7500 or Courtney Harris courtney.harris@fkhealth.com, 617-761-6744

Citation: J. National Cancer Inst. : (December 21, 2005)

Janet Rettig Emanuel | EurekAlert!
Further information:
http://www.yale.edu

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>