Alterations in four proteins involved in apoptosis linked to recurrence rate and poorer survival.
Altered expression of four apoptosis biomarkers may enable more accurate outcome predictions in patients with bladder cancer and identify those who could benefit from adjuvant chemotherapy.
Investigators at the University of Texas Southwestern Medical Center in Dallas performed immunohistochemical staining on four proteins involved with apoptosis—Bcl-2, caspase-3, P53, and surviving—from radical cystectomy specimens of 226 bladder cancer patients. Expression of Bcl-2, caspase-3, P53, and surviving was altered in 73 (32%), 111 (49%), 120 (53%), and 141 (64%) patients, respectively.
After a median follow-up of 36.9 months, patients who showed no alterations in the four biomarkers had a 90% chance of survival at seven years compared with less than 10% if they had four altered biomarkers, the investigators reported in The Lancet Oncology (2007;8:128-136). In addition, combining the four biomarkers with standard outcome predictors such as malignancy stage enhanced predictive accuracy.
The study is the first to measure a combination of apoptosis biomarkers, said urology resident Jose Karam, MD, the lead author. “The exciting thing about our findings is that any practitioner can use this biomarker test. After future validation, clinicians could easily test for the alterations in these biomarkers and it would be simple and relatively inexpensive to perform.”
He added: “Patients who have alterations of all four biomarkers might benefit from adjuvant che-motherapy, even if the cancer appears to be confined to their bladder. Otherwise, their chances for survival are likely to be poor. Likewise, those with no biomarker alterations might not need unnecessary chemotherapy.”
Although the new findings are preliminary and require validation, the study is an important first step, said Robert G. Uzzo, MD, director of Urologic Research at Fox Chase Cancer Center and associate professor of urology at Temple University School of Medicine in Philadelphia. The four markers, he noted, may be useful in clinical trials to help better identify populations that may need more treatment.