Radiation Oncology, Provincial Prostate Brachytherapy Program, Vancouver Cancer Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
Int J Radiat Oncol Biol Phys. 2013 Aug 1;86(5):829-34. doi: 10.1016/j.ijrobp.2013.04.011. Epub 2013 May 18.
To explore whether DNA ploidy of prostate cancer cells determined from archived transrectal ultrasound-guided biopsy specimens correlates with disease-free survival.
Forty-seven failures and 47 controls were selected from 1006 consecutive low- and intermediate-risk patients treated with prostate (125)I brachytherapy (July 1998-October 2003). Median follow-up was 7.5 years. Ten-year actuarial disease-free survival was 94.1%. Controls were matched using age, initial prostate-specific antigen level, clinical stage, Gleason score, use of hormone therapy, and follow-up (all P nonsignificant). Seventy-eight specimens were successfully processed; 27 control and 20 failure specimens contained more than 100 tumor cells were used for the final analysis. The Feulgen-Thionin stained cytology samples from archived paraffin blocks were used to determine the DNA ploidy of each tumor by measuring integrated optical densities.
The samples were divided into diploid and aneuploid tumors. Aneuploid tumors were found in 16 of 20 of the failures (80%) and 8 of 27 controls (30%). Diploid DNA patients had a significantly lower rate of disease recurrence (P=.0086) (hazard ratio [HR] 0.256). On multivariable analysis, patients with aneuploid tumors had a higher prostate-specific antigen failure rate (HR 5.13). Additionally, those with "excellent" dosimetry (V100 >90%; D90 >144 Gy) had a significantly lower recurrence rate (HR 0.25). All patients with aneuploid tumors and dosimetry classified as "nonexcellent" (V100 <90%; D90 <144 Gy) (5 of 5) had disease recurrence, compared with 40% of patients with aneuploid tumors and "excellent" dosimetry (8 of 15). In contrast, dosimetry did not affect the outcome for diploid patients.
Using core biopsy material from archived paraffin blocks, DNA ploidy correctly classified the majority of failures and nonfailures in this study. The results suggest that DNA ploidy can be used as a useful marker for aggressiveness of localized prostate cancer. A larger study will be necessary to further confirm our hypothesis.
探讨经直肠超声引导前列腺穿刺活检标本中前列腺癌细胞的 DNA 倍性是否与无病生存率相关。
从 1006 例低危和中危患者(1998 年 7 月至 2003 年 10 月接受前列腺 125I 近距离放疗)中选择 47 例失败和 47 例对照。中位随访时间为 7.5 年。10 年无病生存率为 94.1%。采用年龄、初始前列腺特异性抗原水平、临床分期、Gleason 评分、激素治疗和随访(均 P 非显著性)进行配对。78 例标本成功处理;27 例对照和 20 例失败标本中含有 100 多个肿瘤细胞,用于最终分析。使用 Feulgen-Thionin 染色的存档石蜡块细胞学样本,通过测量积分光密度来确定每个肿瘤的 DNA 倍性。
将样本分为二倍体和非整倍体肿瘤。20 例失败中有 16 例(80%)和 27 例对照中有 8 例(30%)为非整倍体肿瘤。二倍体 DNA 患者的疾病复发率显著较低(P=.0086)(危险比[HR]0.256)。多变量分析显示,非整倍体肿瘤患者前列腺特异性抗原失败率较高(HR5.13)。此外,V100>90%(D90>144Gy)的“优秀”剂量学患者复发率显著较低(HR0.25)。所有非整倍体肿瘤且剂量学分类为“不佳”(V100<90%;D90<144Gy)(5/5)的患者均出现疾病复发,而非整倍体肿瘤且剂量学分类为“优秀”(8/15)的患者复发率为 40%。相反,剂量学对二倍体患者的结果没有影响。
使用存档石蜡块的核心活检材料,DNA 倍性正确分类了本研究中的大多数失败和非失败患者。结果表明,DNA 倍性可用作局部前列腺癌侵袭性的有用标志物。需要进一步的更大规模研究来进一步证实我们的假设。