Translational Research – What is it?
Translational research is the process of getting basic scientific research findings into the clinical practice or simply put, from lab bench to hospital bedside1. Quite often scientific research findings fall by the wayside and never reach the point where they influence clinical practice. This is usually because the significance of the discovery has not been fully explained to the clinicians, or the discovery has yet to find its place in the clinical setting.
Translational research therefore involves promoting the benefits of a scientific discovery to the medical and scientific community and the general community.
 |
Translational research and colorectal cancer
The Colorectal Cancer Research Consortium (CCRC) has chosen the discovery of the mismatch repair genes, as a significant scientific research discovery that could be incorporated into clinical practice to improve patient outcomes. There are four main mismatch repair genes known as MLH1, PMS2, MSH2 and MSH6. When DNA (the building blocks of cells) replicates, these genes are responsible for correcting any mistakes that occur in the replication process. Scientists have shown that in 15% of colorectal cancers, one or more of these genes are missing. This loss of a gene means that the mistakes in the DNA are not corrected and are subsequently passed onto new cells. Microsatellite DNA are short repetitive strands of DNA that are prone to transcription errors when DNA replicate. When the mismatch repair genes are absent, microsatellite DNA can become irregular in size and an accumulation of these uncorrected DNA strands can lead to the development of cancer. Tumours where the microsatellite DNA are irregular are known as microsatellite unstable tumours.
In a few colorectal cancer patients (~2%), the mismatch repair genes are absent because they were not passed on from one or both parents. This hereditary condition is known as hereditary non-polyposis colorectal cancer (HNPCC). Additional information on this condition and other hereditary cancers can be found on the NSW Cancer Council website. Patients with HNPCC have a higher risk of developing colorectal cancer and other forms of cancer during their lifetime. They are also more likely to develop the cancer at an earlier age (less than 50 years old). |
How are mismatch repair deficient colorectal cancers identified?
When a patient undergoes colorectal cancer surgery, the cancerous tissue is removed and sent to a pathology laboratory to be examined. Part of the tissue sample undergoes a test called immunohistochemistry (IHC). This test specifically looks for the mismatch repair genes. In a normal result, all the genes can be detected, whilst in an abnormal result, one or more of the genes is absent.
Another test that can be conducted in the laboratory is microsatellite instability testing (MSI). Instead of looking for the presence or absence of the mismatch repair genes, this test sees whether the microsatellite DNA strands have become irregular in size due to the absence of the mismatch repair genes. If the microsatellite DNA strands are irregular, the tumour tissue is known as microsatellite unstable tumour. If the mismatch repair genes are present, MSI testing would find that the DNA strands are regular in size which is known as microsatellite stable tumour. We are currently using MSI testing to verify any abnormal IHC results.
Once a patient has been found to have an abnormal IHC result and/or a microsatellite unstable tumour, further testing can following to determine whether the cancer was hereditary.
Pathway for the determination of mismatch repair deficiency cancer
Why distinguish patients without mismatch repair genes?
The CCRC have developed a study to distinguish patients with mismatch repair deficient (MMRD) colorectal cancer from patients whose cancer was caused by other factors. There are several reasons why the identification of MMRD colorectal cancer patients is important. Firstly, patients with a mismatch repair deficient colorectal cancer may require different treatment. Secondly, we would like to identify patients with HNPCC. By identifying HNPCC patients, we can refer them to a Family Cancer Clinic, who will be able to provide genetic counseling. The Family Cancer Clinic will be able to assist with further testing and provide advice on early diagnosis for family members.
We anticipate that at the conclusion of the study, the process of testing for the mismatch repair genes will become part of the standard of care for patients with colorectal cancer.
1. Ioannidis JPA. Materializing research promises: opportunities, priorities and conflicts in translational medicine. Journal of Translational Medicine 2004;2(5).