基于249例移行细胞癌的流式细胞术分析评估DNA含量在膀胱癌中的预后意义

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

作者信息

Vindeløv L L, Christensen I J, Engelholm S A, Guldhammer B H, Højgaard K, Sørensen B L, Wolf H

机构信息

Department of Haematology University Hospital Rigshospitalet, Copenhagen, Denmark.

出版信息

Cytometry. 1995 Jun 15;22(2):93-102. doi: 10.1002/cyto.990220204.

DOI:10.1002/cyto.990220204

PMID:7587754

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 < or = 1.02, P = 0.02), hypotetraploidy (1.50 < DI < or = 1.96, P = 0.002), 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 = 0.05), 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 = 1.70), T-classification (RR = 1.60), and grade (RR = 0.65) as independent prognostic parameters for survival of RT-treated patients.

摘要

在一项对249例新诊断的膀胱移行细胞癌的前瞻性研究中，评估了通过流式细胞术DNA分析确定的DNA指数（DI）、S期分数和异质性的预后意义。中位观察时间为4.8年。共检测到456个亚群。在299个亚群中可以估计S期。DI>1.25或S期高于9.7%与侵袭性密切相关。110例患者接受了经尿道切除术（TUR）。DNA衍生参数无法预测无复发生存率。生存的单因素分析显示二倍体（0.98<DI≤1.02，P=0.02）、低四倍体（1.50<DI≤1.96，P=0.002）和S期大小（P=0.008）具有预后意义。多因素分析指出T分期（RR=1.64）和低四倍体（RR=1.57）是TUR治疗患者生存的预后参数。139例患者接受了放射治疗（RT）。对于具有超四倍体DNA含量亚群的肿瘤（DI>2.04，P=0.05），发现反应明显更好；对于最大S期>24.5%的亚群，反应明显更差（P=0.04）。T分期和组织学分级没有预测价值。逻辑回归分析表明，对于DI>2.04且S期<24.5%的肿瘤，估计对RT有反应的概率为77%，而DI<2.04且S期>24.5%的肿瘤只有28%的反应概率。S期>24.5%预测的对RT的不良反应转化为较差的生存率，而DI>2.04的患者较好的治疗反应并未导致更长的生存期。多因素分析指出S期（RR=1.70）、T分期（RR=1.60）和分级（RR=0.65）是RT治疗患者生存的独立预后参数。