Department of Molecular Oncology, Barts Cancer Institute, Charterhouse Square, London, EC1M 6BQ, UK.
Virchows Arch. 2012 Aug;461(2):103-7. doi: 10.1007/s00428-012-1259-2. Epub 2012 Jul 6.
In vitro studies have implicated neuroendocrine differentiation in the development of hormone resistant prostate cancer following administration of androgen blockers. Studies on clinical material are equivocal. We wished to understand the significance of neuroendocrine differentiation in our large and well-characterised cohort of clinically localised prostate cancer, treated conservatively. Immunohistochemical expression of chromogranin-A was assessed semi-quantitatively on tissue samples of 806 patients in a tissue microarray approach. The correlation of expression with 10-year prostate cancer survival was examined. Multivariate analysis including contemporary Gleason score was performed and sub-group analysis of early hormone treated patients was also undertaken. Chromogranin-A expression correlated with high Gleason score (χ(2) = 28.35, p < 0.001) and early prostate cancer death (HR = 1.61, 95 %CI = 1.15-2.27, p < 0.001). In univariate analysis, NE differentiation correlated significantly with outcome (HR = 1.61, 95 % CI 1.15-2.27, p < 0.001) However in multivariate analysis including Gleason score, chromogranin-A expression was not an independent predictor of survival (HR = 0.97, 95 %CI = 0.89-1.37, p = 0.87). Although chromogranin-A expression was higher in patients with early hormone therapy (χ(2) = 7.25, p = 0.007), there was no association with prostate cancer survival in this sub-group (p = 0.083). Determination of neuroendocrine differentiation does not appear to have any bearing on the outcome of prostatic carcinoma and does not add to the established prognostic model.
体外研究表明，在雄激素阻断剂治疗后，激素抵抗性前列腺癌的发展与神经内分泌分化有关。关于临床标本的研究结果尚无定论。我们希望了解神经内分泌分化在我们大型、特征良好的临床局限性前列腺癌队列中的意义，这些患者接受了保守治疗。采用组织微阵列方法，对 806 例患者的组织样本进行了嗜铬粒蛋白 A 的免疫组织化学表达半定量评估。研究了表达与 10 年前列腺癌生存率的相关性。进行了包括当代 Gleason 评分的多变量分析，并对早期激素治疗患者进行了亚组分析。嗜铬粒蛋白 A 的表达与高 Gleason 评分（χ²=28.35，p<0.001）和早期前列腺癌死亡（HR=1.61，95%CI=1.15-2.27，p<0.001）相关。在单变量分析中，NE 分化与结局显著相关（HR=1.61，95%CI 1.15-2.27，p<0.001）。然而，在包括 Gleason 评分的多变量分析中，嗜铬粒蛋白 A 的表达不是生存的独立预测因子（HR=0.97，95%CI=0.89-1.37，p=0.87）。尽管在早期激素治疗的患者中嗜铬粒蛋白 A 的表达更高（χ²=7.25，p=0.007），但在该亚组中与前列腺癌的生存无关（p=0.083）。神经内分泌分化的测定似乎对前列腺癌的结局没有任何影响，也不会增加既定的预后模型。
