Genitsch Vera, Zlobec Inti, Seiler Roland, Thalmann George N, Fleischmann Achim
Institute of Pathology, University of Bern, Bern 3008, Switzerland.
Department of Urology, University of Bern, Bern 3010, Switzerland.
Int J Mol Sci. 2017 Jul 28;18(8):1640. doi: 10.3390/ijms18081640.
Neuroendocrine serum markers released from prostate cancers have been proposed for monitoring disease and predicting survival. However, neuroendocrine differentiation (NED) in various tissue compartments of metastatic prostate cancer is poorly described and its correlation with specific tumor features is unclear. NED was determined by Chromogranin A expression on immunostains from a tissue microarray of 119 nodal positive, hormone treatment-naïve prostate cancer patients who underwent radical prostatectomy and extended lymphadenectomy. NED in the primary cancer and in the metastases was correlated with tumor features and survival. The mean percentage of NED cells increased significantly ( < 0.001) from normal prostate glands (0.4%), to primary prostate cancer (1.0%) and nodal metastases (2.6%). In primary tumors and nodal metastases, tumor areas with higher Gleason patterns tended to display a higher NED, although no significance was reached. The same was observed in patients with a larger primary tumor volume and higher total size and number of metastases. NED neither in the primary tumors nor in the metastases predicted outcome significantly. Our data suggest that (a) increasing levels of neuroendocrine serum markers in the course of prostate cancer might primarily derive from a poorly differentiated metastatic tumor component; and (b) NED in conventional hormone-naïve prostate cancers is not significantly linked to adverse tumor features.
前列腺癌释放的神经内分泌血清标志物已被提议用于监测疾病和预测生存情况。然而,转移性前列腺癌各个组织区域中的神经内分泌分化(NED)情况鲜有描述,其与特定肿瘤特征的相关性也不明确。通过对119例接受根治性前列腺切除术和扩大淋巴结清扫术、未经激素治疗、淋巴结阳性的前列腺癌患者的组织微阵列免疫染色检测嗜铬粒蛋白A的表达,来确定NED。原发性癌和转移灶中的NED与肿瘤特征及生存情况相关。NED细胞的平均百分比从正常前列腺腺体(0.4%)、原发性前列腺癌(1.0%)到淋巴结转移灶(2.6%)显著增加(<0.001)。在原发性肿瘤和淋巴结转移灶中,Gleason分级较高的肿瘤区域往往显示出较高的NED,尽管未达到显著水平。在原发性肿瘤体积较大、转移灶总体积和数量较多的患者中也观察到同样情况。原发性肿瘤和转移灶中的NED均未显著预测预后。我们的数据表明:(a)前列腺癌病程中神经内分泌血清标志物水平升高可能主要源于低分化的转移瘤成分;(b)未经激素治疗的传统前列腺癌中的NED与不良肿瘤特征无显著关联。