New Tissue Chip to Illuminate the Cancer Development Process
BETHESDA, Md. - Some cancer patients respond well to a particular cancer therapy or combination of therapies. Others do not, but may respond to a different treatment. If doctors knew how to tell those patients apart, they could individualize treatment by designing an optimum therapy for each cancer patient.
Scientists at the National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH), in collaboration with the University of Tampere in Finland and the University of Basel in Switzerland, are developing a new research tool, which they call the "tissue chip," that they expect will eventually help clinicians design such individual treatment plans.
The chip technology, they believe, will illuminate the process of cancer development. Such detailed new information can then be used to identify critical molecules for development of cancer therapies. They also hope the tissue chip will help them learn how to distinguish among subgroups of cancer patients and eventually predict which ones will respond to specific therapies.
"Traditionally, pathology laboratories have analyzed patient tissues one specimen at a time," said Dr. Jeffrey Trent, scientific director of NHGRI's Division of Intramural Research. "However, this new technology now makes it possible to test thousands of specimens simultaneously The power of this technology will accelerate numerous areas of research, including testing of newly isolated genes to determine if they may be of clinical utility as molecular cancer markers."
Like the DNA chip, which scans the genome for alterations or abnormal gene expression, the tissue chip is a microarray that permits massive parallel processing of biological samples. But unlike the DNA chip, the tissue chip makes it possible for researchers to simultaneously compare a variety of molecular markers -- DNA, RNA, and protein -- in cancer tissues from hundreds or thousands of patients. The scientists report that as many as 1,000 tissue biopsies from individual tumors can be studied in a single tumor tissue microarray.
In their initial study of breast cancer tissue microarrays, published in the July issue of Nature Medicine, the researchers analyzed six gene amplifications and expression of the p53 and estrogen receptor genes believed to play a role in breast cancer.
The biopsies from up to 1,000 tumors are embedded and arrayed in paraffin to create a tissue microarray. This tissue array is sliced like a loaf of raisin bread into remarkably thin sections with each of the 1,000 tumors then being represented as minuscule dots on ordinary glass microscope slides. Because each array can be sliced into 200 consecutive sections of 5 micrometers each, it is possible to quickly analyze hundreds of molecular markers in the same set of specimens.
"Our analysis of eight cancer markers was completed in about one week." said Dr. Olli-P Kallioniemi, of NHGRI's Cancer Genetics Branch, the paper's corresponding author. "With traditional methods, going through the specimens one at a time would have taken from 6 to 12 months to analyze them all."
Kallioniemi emphasizes that the tissue chip is a tool for research, not diagnosis. It will be used to identify better diagnostic markers for distinguishing cancer from normal tissue, better markers to predict how aggressive a tumor will be, and biological properties of particular tumors that might have therapeutic value.
The tissue chip is expected to be particularly useful in analyzing the thousands of tumor tissue samples stored in pathology labs all over the world. "It's just not imaginable to stain and analyze thousands of archived tumor tissue samples for hundreds of molecular markers -- one at a time. Now with the tissue chip pathologists can take their existing archives, turn them into tumor arrays, and analyze an entire archive with just a few experiments," said Dr. Juha Kononen, also of the NHGRI and the first author on the paper.
Tissue chips could also help molecular biologists identify novel molecular pathways that play a role in cancer development. This is important in order to be able to design treatment methods specifically targeted against these critical pathways.
Pathologists can also array archived tissue samples from clinical trials of existing cancer drugs, and look for markers--a gene expression pattern or set of genetic changes in the tissue -- associated with whether or not a specific participant in the trial responded to the therapy. Eventually clinicians might be able to use those results to design individual treatments, comparing tumor tissue from a current patient with the historical samples in order to predict how quickly the tumor will progress and which therapeutic approach is likely to work best.
NHGRI oversees the NIH's role in the Human Genome Project, an international research effort to develop tools for gene discovery.
Last Reviewed: February 28, 2012