The researchers, based at the Ludwig Center at the University of
Chicago, found that detection of poorly differentiated basal tumor cells
in early stage cancers; overexpression in those cells of a gene known
as cell division cycle 25C, which plays a key role in the regulation of
cell division; or the ability of tumor fragments to grow when
transplanted into a mouse, all predicted an increased risk of death.
‘Tumor cells collected during the removal of a cancerous bladder and - in some cases - transplanted into mice with weakened immune systems, could help physicians rapidly identify high-risk cancers.’
"If confirmed in larger studies, our findings could help physicians
get a better handle on how a patient's bladder cancer is likely to
progress and allow them to personalize treatment based on that
knowledge," said study author Ralph Weichselbaum, the Daniel K.
Ludwig Distinguished Service Professor of Radiation and Cellular
Oncology and Chair of the Department of Radiation and Cellular Oncology
at the University.
Weichselbaum and colleagues obtained tumor samples from 71 bladder
cancer patients treated at the University and used flow cytometry to
isolate and count specific subtypes of tumor cells in each sample. They
showed that an excess of one relatively rare subtype in early-stage
cancers - the basal tumor cell (BTC) - was associated with a three-fold
increase in risk of death.
Analyzing the global expression of genes in BTCs, the researchers
also identified a potentially prognostic biomarker for bladder cancer:
cell division cycle 25C (CDC25C), a protein that drives cell division.
An expanded analysis, including 400 bladder cancer patients, found that
the expression of this protein is associated with an increased risk of
death even after the removal of the cancerous bladder.
This association disappeared in patients who had previously received
chemotherapy. A test for CDC25C could, the authors suggest, help
determine whether a bladder cancer patient is likely to benefit from
drug treatment.
In more invasive tumors, the presence and number of BTCs had less
prognostic value. When the researchers injected bladder-cancer tissue
fragments from 69 patients with more advanced cancers into the flanks of
immune-deficient mice, however, about 60% of these tumor
fragments were able to take hold and grow in this setting. This was
associated with a six-fold increase in risk of death, compared to tumor
fragments that did not survive and grow after transplantation.
"Prognostic knowledge can change a lot about how you choose to treat
a cancer," said Weichselbaum. "We may be able to avoid aggressive
measures if we find a tumor has relatively few basal cells," he said.
"We could treat an early-stage bladder cancer with less aggressive
therapy, avoiding debilitating interventions like radical cystectomy.
But if a bladder tumor has a lot of basal cells, we may need to take the
entire bladder out and follow that with chemotherapy.
Before this can happen, he added, the accuracy of his team's new
prognostic model and biomarker "will need to be confirmed in larger
studies."
Source: Eurekalert
