Prostate cancer affects the lives of thousands of men across Europe. The earlier it can be detected, the higher the chance of a full recovery following treatment.
Work funded through the predecessor of the Standards, Measurement and Testing Programme
has provided laboratories with a reference material to help them accurately and reliably detect subtle changes in patients' enzyme levels. This way the disease is easier to diagnose and monitor.
Testing body fluids and tissues for the presence of enzymes provides a well-established tool for doctors to diagnose prostate cancer patients. Levels of enzymes, proteins in the body which catalyse biological reactions, can be monitored to see the effect of treatment. It is obvious that inaccurate measurements can have drastic consequences on the patient's health. Unnoticed disease symptoms can cause treatment to be delayed, at which point it is often too late.
The enzyme level is measured in terms of the enzyme's catalytic activity, which is the rate at which a specific biological process converts one chemical into another. This property of the enzyme depends not only on the amount of active enzyme present but also on factors such as temperature and pH. With many reactions, the reactions are fastest at optimum temperature 37°C, the temperature of the human body.
Consequently, if results are to be comparable from one laboratory to the next, it is vital that the experimental conditions are recorded and accounted for in the results.
Improving enzyme detection and measurement
Over the last two decades, much work has been done to standardise the methods used to measure enzyme catalytic activity. This has gone a long way in improving the comparability of results between laboratories but what was also needed was a certified reference material (CRM). This CRM has now been developed and produced by a team of nine laboratories and it is available to all medical testing institutions, universities and medical equipment manufacturers. What it allows, which was impossible before, is new or adapted measurement methods to be checked and verified for accuracy. This means that alternative methods and their results can be traced to the official method and thus, measurements can easily be compared.
Enzyme measurement work with the Standards, Measurement and Testing Programme, then known as the BCR, began as long ago as 1980. Expert clinical enzymologists prepared and tested reference samples of several enzymes to accurately determine these materials' enzyme activities. Analysis skills were vastly improved and the medical world gained useful tools. An important general point that emerged from this "enzyme programme" is that enzyme preparations can be stable under suitable conditions for several years. The instability of enzymes was, in the past, thought to be a barrier to the production of CRMs.
A need emerged for a CRM to specifically aid prostate cancer diagnosis. The prostate gland, which is associated with the production of sperm in men, secretes an enzyme called prostatic acid phosphatase (PAP). In all stages of prostate cancer, except the final stages, PAP levels are raised compared to those of healthy individuals. This fact has been used to detect prostate cancer for over half a century, but the sensitivity of the measurements has been markedly improved and the correlation between PAP levels and the extent of cancer, are now better understood.
Developing the reference material, which is based on extracts from routine autopsies on healthy men, presented many technical hurdles. The samples were purified after all extracts containing communicable diseases such as HIV and hepatitis were discarded. This was crucial because many analysts around Europe would be using the material and accidental infection through the reference material must definitely be avoided.
Three thousand samples prepared
A batch of three thousand samples was prepared. It was important to make sure that each of them contained the same levels of PAP and that these levels remained constant over time. These stability and homogeneity tests were carried out in the UK.
The absolute and accurate measurements on the samples were then carried out. In order to perform these investigations, the laboratories - experts in clinical chemistry from seven European countries - had to scrutinise their methods and results together to come to an agreed value for the enzyme measurement. They tested their methods through these interlaboratory studies and found one with sufficient reliability and robustness for assigning a value to the PAP level.
Prior to final certification, the reference material was tested in medical testing laboratories to make sure that the CRM would be a useful tool in practice as well as in theory. Laboratories participating in the UK External Quality Assessment Scheme in Clinical Chemistry received a sample to measure for PAP. The results of these laboratories show that the material has in fact helped harmonise results even though variations of the methods are often used.
Earlier cancer detection achieved
The material has improved the consistency of the measurements used for prostate cancer diagnosis across the European Community. This in turn may enable as many sufferers as possible to receive prompt treatment.
As well as developing a material to help reliably confirm early stages of the cancer, the laboratories who participated in this project also benefited from the work. Not only did they have the chance to work with other European experts in their field, but they also formed a network of laboratories. This network provides support to its members when a new method needs to be tested and when other measurement difficulties arise.