Lessard Laurent, Karakiewicz Pierre I, Bellon-Gagnon Pascale, Alam-Fahmy Mona, Ismail Hazem A, Mes-Masson Anne-Marie, Saad Fred
Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Institut du Cancer de Montréal, and the Department of Surgery/Urology, CHUM, University of Montréal, 1560 rue Sherbrooke est, Montréal, Québec, Canada.
Clin Cancer Res. 2006 Oct 1;12(19):5741-5. doi: 10.1158/1078-0432.CCR-06-0330.
Lymph node invasion (LNI) is associated with increased risk of prostate cancer progression. Unfortunately, pelvic lymph node dissections are fraught with a high rate of false-negative findings, emphasizing the need for highly accurate markers of LNI. Because nuclear factor-kappaB (NF-kappaB) is a candidate marker of prostate cancer progression, we tested the association between nuclear localization of NF-kappaB in radical prostatectomy specimens and the presence of LNI.
NF-kappaB expression in radical prostatectomy specimens was assessed with a monoclonal NF-kappaB p65 antibody, in 20 patients with LNI and in 31 controls with no LNI and no biochemical relapse 5 years after radical prostatectomy. Univariate and multivariate logistic regression models were used. The accuracy of multivariate predictions with and without NF-kappaB was quantified with the area under the receiver operating characteristics curve and 200 bootstrap resamples were used to reduce overfit bias.
Univariate regression models showed a 7% increase in the odds of observing LNI for each 1% increase in NF-kappaB nuclear staining (odds ratio, 1.07; P = 0.003). In multivariate models, each 1% increase in NF-kappaB was associated with an 8% increase in the odds of LNI (odds ratio, 1.08; P = 0.03) and its statistical significance was only surpassed by the presence of seminal vesicle invasion (P = 0.003). Addition of NF-kappaB to all other predictors increased the accuracy of LNI prediction by 2.3% (from 84.8% to 87.1%; P < 0.001).
This is the first study that shows that the extent of nuclear localization of NF-kappaB in primary prostate tumors is highly accurately capable of predicting the probability of locoregional spread of prostate cancer.
淋巴结浸润（LNI）与前列腺癌进展风险增加相关。遗憾的是，盆腔淋巴结清扫术存在较高的假阴性率，这凸显了对LNI高度准确标志物的需求。由于核因子-κB（NF-κB）是前列腺癌进展的候选标志物，我们检测了根治性前列腺切除标本中NF-κB的核定位与LNI存在之间的关联。
使用单克隆NF-κB p65抗体评估根治性前列腺切除标本中的NF-κB表达，研究对象为20例有LNI的患者以及31例无LNI且根治性前列腺切除术后5年无生化复发的对照者。采用单变量和多变量逻辑回归模型。通过受试者操作特征曲线下面积对有无NF-κB的多变量预测准确性进行量化，并使用200次自抽样重采样以减少过拟合偏差。
单变量回归模型显示，NF-κB核染色每增加1%，观察到LNI的几率增加7%（比值比，1.07；P = 0.003）。在多变量模型中，NF-κB每增加1%，LNI的几率增加8%（比值比，1.08；P = 0.03），其统计学意义仅被精囊浸润的存在所超越（P = 0.003）。将NF-κB添加到所有其他预测因子中，LNI预测的准确性提高了2.3%（从84.8%提高到87.1%；P < 0.001）。
这是第一项表明原发性前列腺肿瘤中NF-κB核定位程度能够高度准确预测前列腺癌局部区域扩散概率的研究。
