Cancer screening
MRC researchers have found markers for cancer cells that may help detect thousands of new cases of cancer a year. The markers are already part of an MRC-developed device that screens for cancer of the oesophagus, are being trialled for cervical cancer screening and could potentially be used in a test for bowel cancer.
Researchers at the MRC Cancer Cell Unit in Cambridge have, for a long time, been identifying the genes and proteins that cause cancer cells to be different from non-cancer cells, which could be used as distinguishing markers.
In the 1990s, Professor Ron Laskey at the unit identified certain proteins that are needed in order for DNA to be copied, during what is known as the ‘cell cycle’. Cancer cells remain in the cell cycle when they shouldn’t be, therefore proteins involved in the replication process would serve to identify these cells.
Along with other teams around the world, Professor Laskey’s group found specific proteins, called minichromosome maintenance proteins (MCMs), which are abundant in cells from cancers and absent from almost all normal cells1. Other less-effective markers were also found, but the MCM proteins are superior because they are present throughout the cell cycle and are more abundant, stable and distinguishable.
Markers put to clinical use
Late in the 1990s, another team at the unit, led by Dr Nicholas Coleman, began to consider MCMs for clinical use in either a diagnostic or screening test for cervical cancer2. They were granted a patent for this and licensed the technology to a company, Tripath Imaging, which has been acquired by Becton, Dickinson and Company.
The old screen for cervical cancer – which is still in practice – does not use markers, but involves manual inspection of samples. Currently, millions of pounds are spent to save roughly 1,000 lives a year in the UK. An automatic test, such as one for MCMs, would cost much less. Tripath Imaging is running large multicentre trials in the US and Canada involving up to 25,000 women, which will reveal the performance of MCMs and also how readily they can be read by machines. The test will be useful even when there is a vaccine for cervical cancer; there will still be a small number of cases, which could be missed without a reliable test.
A test for many cancers
The team has also shown that the markers could be used to detect other types of cancers. The technique is being developed on a large scale to provide a test for bowel cancer, which is an improvement on the current method3. Also, Dr Rebecca Fitzgerald’s group at the MRC Cancer Cell Unit has filed a patent for a non-invasive device to screen for a condition called Barrett’s Oesophagus, which is a risk factor for cancer and occurs when acid in the stomach causes changes to the structure of the oesophagus tissue4.
Cancer of the oesophagus is becoming more widespread, but the majority of patients with this condition are undiagnosed. Only 20 per cent of people with Barrett’s oesophagus are currently detected, but they have a much greater risk of cancer than the general population, equivalent to a risk of 1 per cent a year.
Population screening by endoscopy – inserting a tube with optical fibres for viewing – would be expensive and impractical. The new test simply requires the patient to swallow a sampling sponge on the end of a string. The device itself is used to collect cells to examine them; in Barrett’s, the tissue looks different and can be identified visually. Then the team applies a stain to the cells which detects MCM proteins and hence either Barrett’s or cancer. The test will be introduced into primary care in March 2007 as a trial, and rated on its detection success. In the future, the device could be used to screen men over 50 with heartburn, a high risk group.
MCM markers also have the potential to be used in a screen for oral cancer5. Up to 500,000 new cases of mouth and throat cancer are diagnosed annually and approximately 75 per cent of these occur in the developing world. A test for the markers would be non-invasive, accurate, quick and cheap.
References
1. Madine et al. (1995). The nuclear envelope prevents reinitiation of replication by regulating the binding of MCM3 to chromatin in Xenopus egg extracts. Current Biology, 5, 1270.
2. Gonzalez et al. (2005). Control of DNA replication and its potential clinical exploitation. Nature Reviews Cancer, 5, 135.
3. Scott et al. (2003). A novel immunohistochemical method to estimate cell-cycle phase distribution in archival tissue: implications for the prediction of outcome in colorectal cancer. Journal of Pathology, 1, 187.
4. Lao-Sirieix et al. (2004). Cell cycle phase abnormalities do not account for disordered proliferation in Barrett’s carcinogenesis. Neoplasia, 6, 751.
5. Scott et al. (2006). A minimally invasive immunocytochemical approach to early detection of oral squamous cell carcinoma and dysplasia. British Journal of Cancer, 94, 1170.
MRC, January 2007