Screening for cancerous growths in the body can involve considerable discomfort for patients. But a researcher at University College Dublin (UCD) is now looking at a biochemical marker that could help predict from the outset whether patients with primary bladder cancer will go on to develop a more invasive form of the disease.
Her work could ultimately reduce the need to do uncomfortable follow-up screens on low-risk patients.
Every year about 463 people in Ireland are diagnosed with bladder cancer. And for almost a third of patients the cancer will spread further, even if the primary tumour is removed.
"There's a very high recurrence risk generally for bladder-cancer patients and we're trying to find a way to identify which of those patients will get invasive disease in the future," says Dr Amanda McCann, a senior lecturer at UCD's school of medicine and medical science.
The current method to assess a patient for tumour regrowth inserts a cystoscope into the urethra, an uncomfortable process. Dr McCann is now looking at a potential new "biomarker" that could rapidly identify tumours with a high risk of invasion simply by testing the removed tissue.
She is focusing on a protein called alpha-T-catenin that helps to anchor cells together. Falling levels of this protein mean that cells could be gaining the ability to move away from the parent tumour and invade surrounding muscle, or to get into the circulation and seed tumours elsewhere in the body, explains McCann.
At the Conway Institute, McCann and PhD student Maria Meehan extracted genetic material from excised tumour samples, and discovered that in a proportion of tumours the gene for alpha-T-catenin had become "imprinted", meaning that only one copy of the gene was switched on, instead of the usual two.
"We genetically inherit one complete set of information from both our parents, so at the DNA level we have a duplicate of everything," explains McCann, who receives funding from Cancer Research Ireland. "But with imprinted genes we have the genetic contribution from each parent but only one parent's copy is actually active. Alpha-T-catenin is not imprinted in adult tissue - there are two copies expressed - but in tumourigenic tissue it reverts back to expressing one copy."
McCann's team now wants to look at levels of alpha-T-catenin protein in bladder tumours and compare the results with patient outcome, to see if a simple test for alpha-T-catenin levels in the original tumour can predict future invasiveness.
To speed up the screening process they are using tissue microarrays in collaboration with Prof Elaine Kay from Beaumont Hospital. She will now use specific antibodies to measure levels of alpha-T-catenin in tissue microarrays from 350 consenting bladder-cancer patients who attended Prof John Fitzpatrick at the Mater Misericordiae Hospital.
Clinical data associated with each sample will allow Dr McCann to compare alpha-T-catenin levels with what later happened to the patient. "We started recruiting these patients from 1990, so we have 15 years of follow-up," she says.
If low alpha-T-catenin levels in a tumour sample are linked with future invasiveness, it could provide a simple screen to assess a patient's future risk and manage any follow-ups accordingly, explains McCann. And she hopes that measuring biomarkers might become even easier. "It would be ideal if patients could give a urine sample, test that can see if the tumour has come back or become more aggressive," she says.
On Tuesday, Dr McCann gave a talk about her work at UCD to launch this year's Cancer Research Ireland Terry Fox Runs to raise funds for cancer research. See www.cancer.ie/terryfox for more details. You can also donate downtime on your PC to help cancer researchers process data from tissue microarray experiments. See
www.cancer.ie/wcg
