Prognostic significance of dna content in bladder cancer based on flow cytometric analysis of 249 transitional cell carcinomas

Abstract

The prognostic significance of DNA index (DI), S-phase fraction, and heterogeneity determined by flow cytometric DNA analysis was assessed in a prospective study of 249 newly diagnosed transitional cell carcinomas of the bladder. The median observation time was 4.8 years. A total of 456 subpopulations were detected. The S-phases could be estimated in 299 subpopulations. A DI > 1.25 or an S-phase above 9.7%were strongly correlated to invasiveness.One hundred and ten patients were treated with transurethral resection (TUR). Relapse-free survival could not be predicted by the DNA-derived parameters. Univariate analysis of survival showed prognostic significance of diploidy (0.98 < DI 5 1.02, P = 0.021, hypotetraploidy (1.50 < DI 5 1.96, P = 0.0021, and S-phase size (P = 0.008). Multivariate analysis pointed to the T-classification (RR = 1.64) and hypotetraploidy (RR = 1.57) as prognostic parameters for survival of TUR-treated patients.One hundred and thirty-nine patients received radiotherapy (RT). A significantly better response was found for tumors with a subpopulation with a hypertetraploid DNA content (DI > 2.04, P = 0.051, and a significantly worse response for subpopulations with a maximum S-phase > 24.5% ( P = 0.04). T-classification and histological grade had no predictive value. A logistic regression analysis indicated an estimated probability of response to RT of 77% for tumors with a DI > 2.04 and an S-phase < 24.5%, whereas tumors with a DI < 2.04 and an S-phase > 24.5% had only a 28% probability of response. The poor response to RT, predicted by an S-phase > 24.5%, translated into a poor survival, whereas the better treatment response found for patients with a DI > 2.04 did not result in a longer survival. Multivariate analysis pointed to S-phase (RR = 1.701, T-classification (RR = 1.601, and grade (RR = 0.65) as independent prognostic parameters for survival of RT-treated patients. o 1995 Wiley-Liss, Inc.Key terms: Detergent-trypsin preparation, propidium iodide, chicken and trout erythrocyte standardization, multivariate analysis of survival, treatment response Transitional cell carcinoma of the bladder is a disease entity encompassing a wide spectrum of tumors ranging from relatively benign non-invasive neoplasms with a low capacity for progression to rapidly disseminating cancers with a high mortality rate. The best prognostic parameters in general use today are the T-classification and histological grade (9,19,22). These parameters are influenced by the subjectivity of the urologist and the pathologist ( 20) and therefore not completely reproducible. Furthermore considerable variation in the clinical course may be found for tumors of identical class and grade. There is thus a need for additional and preferentially objective measurements with prognostic significance in bladder cancer.The prognostic value of tumor DNA content has been recognised for a number of years (2). Flow cytometric DNA analysis yields information on stem-line DNA abnormality, heterogeneity, and S-phase size. These variables

Prognostic Effect of DNA Aneuploidy from Bladder Washings in Superficial Bladder Cancer

“…Whereas recent studies showed an association between DNA aneuploidy in the resected tumor tissue and progression to invasive cancer (17)(18)(19)(20), none had addressed the prognostic effect of DNA aneuploidy in cells obtained from bladder washings of an endoscopically normal organ. Conceivably, DNA aneuploidy in bladder washing may reflect the presence of T is in bladder mapping, which was not assessed in our study.…”

“…The results of the trial at 12 and 36 months have previously been published (16). Importantly, recent studies have shown that DNA aneuploidy in papillary tumor tissue predicts the subsequent risk of invasive cancer (17)(18)(19)(20).…”

The PTEN regulator DJ‐1 is associated with hTERT expression in clear cell renal cell carcinoma

“…34 A FACScan flow cytometer was used (Becton Dickinson Immunocytometry Systems, San Jose, CA) and the DNA index (DI) was calculated. A tumor was denominated diploid (DI 5 1) when only one peak was detected and aneuploid when two (or more) separate peaks were found.…”

The Prognostic Significance of S&ndash;Phase Analysis in Stage Ta&sol;T1 Bladder Cancer

“…Furthermore, Vindelov et al [14]have shown that response to radiation therapy is better for patients whose superficial bladder cancers have lower S–phase values.…”

“…Several flow cytometric studies of superficial bladder cancer have found tumor proliferation to be a prognostically useful adjunct to DNA ploidy information [11, 12, 13, 14]. However, not all such studies have found significant survival differences between those whose tumors have low or high S–phase fractions [15].…”