Finding altered expression of four key cell cycle regulators, especially when these are viewed in combination, may make it possible for physicians to predict the clinical outcome for transitional cell carcinoma of the bladder following a cystectomy, according to the results of a recent study.
The key cell cycle regulators are p53, p21, pRB and p16, all tumor suppressor genes.
The findings of the study, the first to analyze the four markers in combination in order to get a better picture of bladder cancer prognosis, were published in the March 15 issue of The Journal of Clinical Oncology.
The altered expression of p53 was the strongest sign of cancer progression, followed by the altered expression of p21, thus suggesting that the p53/p21 combination may have a stronger relation with outcome measures than the pRB/p16 combination.
The study also found that the more marker accumulations there are, the more adverse the impact of bladder cancer on progression and mortality.
The study involved the staining of archival tumor specimens for the four cell cycle regulators from 80 individuals with bladder cancer who had undergone a radical cystectomy, or removal of the bladder. The aim of the study was to see if the expression of these regulators is linked with the stage, progression and prognosis of bladder cancer. The patients involved were observed for a median of 101 months.
The study showed that altered expression in the four cell cycle regulators was found in many of the tumors. The investigators noted the independent association of each marker alteration with prognosis, progression and survival following a cystectomy.
Altered expression of p53 was found in 56%, of p21 in 49%, of pRB in 54% and of p16 in 53% of the tumors compared with those found in normal bladder epithelium.
Altered expression was also found in at least one of the tumor suppressor genes in 83% of bladder cancer tumors, with 26% of the tumors having alterations in three of these genes.
A comprehensive six-year study is currently underway to validate these retrospective observations.
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