Blood and Tissue Samples:
Why They Are So Important to Dr. Catalona
by Cecilia Lacks, PhD
Blood and tissue samples from patients serve at least two purposes.
One is to help with the diagnosis and treatment for a particular patient. The PSA test (from a blood sample) and the prostate biopsy (from a tissue sample) are two prime examples.
Another purpose for samples that are collected by a researcher under approved research protocols - one for the long term - is research. In the case of prostate cancer, the blood and tissue samples are used to find genetic causes or predispositions for prostate cancer, to develop better treatments for the disease, and to find improved testing methods for early and reliable diagnosis, and, possibly, to find a means of preventing prostate cancer.
"Blood samples for the purposes of routine diagnosis are usually discarded after they provide the information doctors need for treatment decisions," Dr. Catalona said.
"The doctor who initiates a collection for research creates the blueprint for its use."
Biopsies that have been embedded in paraffin (wax) are often kept for a time in the archives of hospital pathology departments; pretty much to document what was wrong with the patient, i.e., in case someone questioned whether someone really had cancer or not, they could prove it.
These specific biopsy samples are not used for the future medical care of a particular patient.
"On the other hand, blood and tissue samples collected by a researcher for research become more prized and more useful as they become part of a larger collection and have associated follow-up information over many years," he said.
Blood and tissue samples are non-renewable resources. Once they are used up, once the resource is depleted, the research is no longer possible. How to use these samples in the most effective manner is therefore an important decision.
The doctor or researcher who initiates a collection for research also creates the blueprint for its use, thinking about research needs in the future.
Dr. Catalona began collecting blood and tissue samples almost 20 years ago. Thousands of his patients and research participants have entrusted blood and tissue samples to him for his research projects. He has created one of the most useful, and one of the largest, collections in the world for prostate cancer research.
And he has chosen wisely in directing the use of his collection.
Dr. Catalona introduced PSA as a first-line screening test for prostate cancer in 1991. That test dramatically changed the landscape of treatment success for prostate cancer with death rates continually falling since 1995.
"The PSA test isn't perfect," Dr. Catalona said. "We are looking at other forms of PSA to help us lessen the false positives and the false negatives in the testing."
In collaboration with researchers at the Harvard School of Public Health and the Dana Farber Cancer Center, Dr. Catalona's research group has recently had a paper accepted in the New England Journal of Medicine, suggesting that lower PSA cutoffs for prostate biopsy should be considered in every day practice. This research was based upon the results of Dr. Catalona's PSA Study.
Also, Dr. Catalona said that new tests are needed to distinguish between aggressive and non-aggressive forms of prostate cancer.
"We are studying other proteins besides PSA to improve diagnostic procedures," he said.
New work in the above areas relies upon the continued use of the blood samples, collected from his PSA study which began in 1989.
Dr. Catalona is sharing his tissue sample collection and data and collaborating with scientists in many of the most advanced research centers in the United States who are studying the genetics of prostate cancer.
Among the centers are Case Western Reserve, Cleveland Clinic, Harvard, Johns Hopkins, Mayo Clinic, MIT, University of California at San Francisco, University of Pittsburgh, and Washington University.
He and his collaborators have conceived specific research projects that require these samples, and he has chosen well in directing the use of his collection for genetic research.
At a recent CaP CURE conference, Dr. Catalona presented summaries of recent genetic studies conducted by his collaborative prostate cancer research group. (see fall QUEST 2002).
More than 10 scientific publications have resulted from these studies and numerous discoveries have led to further research. Dr. Catalona's research group has had a significant impact on the research in prostate cancer genetics.
One study, a whole genome linkage study, identified five chromosomal regions that were statistically linked to prostate cancer susceptibility. One of the strongest linkage signals was found on chromosome 16. Subsequent studies from collaborators narrowed this region to an area where genetic losses are found in approximately half of prostate cancer patients.
Linkage studies were also performed to find regions that may be associated with aggressive forms of prostate cancer.
Some of the most exciting findings from Dr. Catalona's collaborative research group are connected to the gene RNAseL, located on chromosome 1, and a variant of this gene, R46Q2, which is associated with increased cancer risk. At least one copy of R462Q is carried by nearly 60% of the men in the study.
"The potential is there for developing clinical tests for prostate cancer susceptibility and possible new methods of prevention and treatment," Dr. Catalona said.
The collaborators in the Harvard/MIT group have just completed the largest study of gene expression profiles of Dr. Catalonas patients who have prostate cancer that has been cured and those who have cancers that have recurred.
Using Dr. Catalona's samples, Dr. Milbrant's laboratory in St. Louis was among the first to find that the gene, hepsin, is over expressed in prostate cancer.
Currently, several pharmaceutical companies are working on developing inhibitors of hepsin as a possible future treatment of prostate cancer.
"Each of these discoveries is a new piece of the puzzle put into place. With each discovery, the big picture becomes clearer and the solution nearer," Dr. Catalona said.
Dr. Catalona's new position, directing the clinical prostate cancer program at Northwestern University's Robert H. Lurie Comprehensive Cancer Center, provides a strong base for his research and for his continued and increased collaboration with scientists across the country and the world.
The blood and tissue samples in his collection continue to be the basis for his research work and for the work of his chosen collaborators.