NF-κB nuclear localization and its prognostic significance in prostate cancer
NF-κB nuclear localization and its prognostic significance in prostate cancer
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DOI：
10.1046/j.1464-410x.2003.04104.x
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发表时间：
2003-03-01
影响因子：
4.5
通讯作者：
Saad, F
中科院分区：
文献类型：
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作者：
Lessard, L;Mes-Masson, AM;Saad, F
目的检测NF-κ B（p65）在不同组织学分级的人前列腺癌组织中的亚细胞定位，并检测NF-κ B单独定位或结合组织学分级是否可用于预测患者预后。患者和方法前列腺癌组织从根治性前列腺切除术标本中获得;使用Gleason分级系统确定组织学分级。临床结果被定义为良好（5年无病生存，前列腺特异性抗原水平检测不到）或差（进展为骨转移）。NF-κ B的亚细胞定位通过免疫组织化学使用抗p65抗体进行可视化。首先在45个样本中评估NF-κ B的亚细胞定位;在这些样本中，NF-κ B的核定位对癌组织是特异性的，但与Gleason评分无关（P = 0.089）。然后评估NF-κ B作为预后标志物，以补充Gleason评分预测癌症进展。纳入了30例已知临床结局的男性患者的肿瘤组织; 17例结局较差的患者中有10例NF-κ B核染色阳性，而13例结局良好的患者中只有2例阳性（P = 0.026）。当结合NF-κ B亚细胞定位和Gleason评分时，定义了两种进展风险类别。结果良好的13例标本中有11例属于低风险类别（Gleason 2-4或Gleason 5-7，核NF-κ B阴性），不良结局组17例中有12例属于高危组。（核NF-κ B阳性的Gleason 8-10或Gleason 5-7;结论：NF-κ B在前列腺癌组织中的表达可在细胞核中检测到，其阳性表达可用于预测患者预后。使用其他临床和分子变量的多变量分析正在进行中，并将验证NF-κ B作为预后因子的有用性。
OBJECTIVETo detect the subcellular localization of NF-kappaB (p65) in human prostate cancer tissues of different histological grades, and to test whether NF-kappaB localization alone, or combined with the histological grade, can be used to predict patient outcome.PATIENTS AND METHODSProstate cancer tissues were obtained from radical prostatectomy specimens; the histological grade was determined using the Gleason grading system. Clinical outcomes were defined as good (5-year disease-free survival with undetectable levels of prostate specific antigen) or poor (progression to bone metastases). The subcellular localization of NF-kappaB was visualized by immunohistochemistry using an anti-p65 antibody.RESULTSThe NF-kappaB subcellular localization was initially assessed in 45 specimens; in these samples a nuclear localization of NF-kappaB was specific to cancer tissues, but did not correlate with the Gleason score (P = 0.089). NF-kappaB was then assessed as a prognostic marker to complement Gleason score in predicting cancer progression. Tumour tissues from 30 men with a known clinical outcome were included; 10 of 17 patients who had a poor outcome were positive for NF-kappaB nuclear staining, whereas only two of 13 with a good outcome were positive (P = 0.026). When NF-kappaB subcellular localization and Gleason score were combined, two risk categories of progression were defined. Eleven of 13 specimens from those with a good outcome were in the low-risk category (Gleason 2-4 or Gleason 5-7 with negative nuclear NF-kappaB) and 12 of 17 in the poor outcome group were in the high-risk category (Gleason 8-10 or Gleason 5-7 with positive nuclear NF-kappaB; P = 0.004).CONCLUSIONNF-kappaB is detectable in the nucleus in prostate cancer tissues and positivity can be used to help predict patient outcome. Multivariate analyses using other clinical and molecular variables are underway, and will validate the usefulness of NF-kappaB as a prognostic factor.