核圆形度变异可预测前列腺癌的进展、转移和死亡：根治性前列腺切除术后长达 25 年的前瞻性评估。

Nuclear roundness variance predicts prostate cancer progression, metastasis, and death: A prospective evaluation with up to 25 years of follow-up after radical prostatectomy.

机构信息

James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.

出版信息

Prostate. 2010 Sep 1;70(12):1333-9. doi: 10.1002/pros.21168.

DOI:10.1002/pros.21168

PMID:20623633

Abstract

BACKGROUND

Nuclear structure is often altered in cancer due to spatial rearrangements of chromatin organization via activation of oncogenes and other chromatin remodeling genes. Therefore, we evaluated the prognostic value of nuclear roundness variance (NRV) for prostate cancer (PCa) progression, metastasis and PCa-specific death free survivals in a cohort of 116 men after radical prostatectomy (RP).

METHOD

NRV was calculated for each case using the variance of the nuclear roundness from approximately 150 nuclei captured at a magnification of 2,440x for each case in 1992-1993. $${\rm Nuclear},{\rm roundness} = {{{\rm Radius}({\rm circumference})} \over {{\rm radius}({\rm area})}} = {R \over r} = {{P/2\pi } \over {\sqrt {A/\pi } }}$$ NRV data were merged with clinical, pathologic, and follow-up data for all patients in 2009. Cox proportional hazards regression and Kaplan-Meier plots were employed to analyze the data.

RESULTS

Median follow-up time after RP for all patients was 19 years (range: 1-25 years, mean: 17 years), with approximately 92% (107/116), 71% (82/116), and 47% (55/116) patients having >or=10, 15, and 20 years of follow-up, respectively. NRV was the most significant parameter for prediction of all three outcomes and its concordance-index (C-Index) increased from progression (0.7080) to metastasis (0.7332) to PCa-specific death (0.8090) free survival predictions. Of note, NRV C-Index was significantly higher compared to Gleason Score C-Index for metastasis (0.7332 vs. 0.6046; P = 0.027) and PCa-specific death (0.8090 vs. 0.6336; P = 0.004) free survival predictions. However, the difference between NRV and Gleason Score C-Indexes was not statistically significant for progression free survival prediction (0.7080 vs. 0.6463; P = 0.106).

CONCLUSION

NRV is valuable nuclear structural feature that exceeds Gleason score to predict an aggressive phenotype of PCa.

摘要

背景

由于染色质组织的空间重排通过激活癌基因和其他染色质重塑基因，核结构在癌症中经常发生改变。因此，我们在 1992-1993 年对每例患者约 150 个核进行放大倍数为 2,440x 的拍摄，计算了每个核的核圆度方差（NRV），以评估其在接受根治性前列腺切除术（RP）的 116 名男性患者中对前列腺癌（PCa）进展、转移和 PCa 特异性死亡无复发生存的预后价值。

方法

使用每个核的核圆度方差来计算 NRV，该方差是从每个核的半径（周长）除以半径（面积）得到的，即$${\rm Nuclear},{\rm roundness} = {{{\rm Radius}({\rm circumference})} \over {{\rm radius}({\rm area})}} = {R \over r} = {{P/2\pi } \over {\sqrt {A/\pi } }}$$ 。在 2009 年，我们将 NRV 数据与所有患者的临床、病理和随访数据合并。采用 Cox 比例风险回归和 Kaplan-Meier 图分析数据。

结果

所有患者 RP 后的中位随访时间为 19 年（范围：1-25 年，平均：17 年），分别约有 92%（107/116）、71%（82/116）和 47%（55/116）的患者随访时间大于等于 10、15 和 20 年。NRV 是预测所有三种结局的最重要参数，其一致性指数（C-Index）从进展（0.7080）到转移（0.7332）到 PCa 特异性死亡（0.8090）无复发生存的预测值增加。值得注意的是，与格里森评分的 C-Index 相比，NRV 的 C-Index 对转移（0.7332 对 0.6046；P = 0.027）和 PCa 特异性死亡（0.8090 对 0.6336；P = 0.004）无复发生存预测具有更高的显著性。然而，NRV 与格里森评分 C-Index 之间的差异在进展无复发生存预测方面没有统计学意义（0.7080 对 0.6463；P = 0.106）。