Cussenot O, Villette J M, Cochand-Priollet B, Berthon P
Department of Urologie, Hôpital Saint Louis, and Université Paris, France.
Prostate Suppl. 1998;8:43-51.
Prostate cancer, like other solid tumors, is a rather heterogeneous entity. More than 50% of all malignant prostatic tumors contain neuroendocrine-like cells, which cannot be attributed to small cell prostatic carcinoma or carcinoid-like tumors, which represent only 1-2% of all prostatic malignancies. Several investigators have reported that histopathologic determination of neuroendocrine differentiation in prostate carcinomas may have prognostic implications, while others have not confirmed these results. However, on the basis of experimental data, neuroendocrine-like cells appear to be involved in the emergence of androgen-independent cells and could be a target for new prostate cancer therapeutic strategies.
The literature on the neuroendocrine phenotype of prostatic carcinoma is reviewed. This review summarizes most of the accumulated experimental and clinical data on the neuroendocrine phenotype in prostate cancer. We analyze the putative functions of neuroendocrine-like cells in prostate cancer progression and discuss the place of neuroendocrine phenotype biomarkers as diagnostic and prognostic factors in prostate cancer.
The fact that focal, patchy and heterogeneous clusters of neuroendocrine-like cells are frequently identified in organ-confined prostatic carcinoma probably accounts for the various evaluations of the predictive value of neuroendocrine histological patterns for the clinical outcome at this stage of the disease. The amount of neuroendocrine cells required to produce a detectable elevation in plasma chromogranin A has not yet been determined, but it is correlated with the number of chromogranin A-positive neuroendocrine (NE) cells. Despite the obvious current limitations of the application of neuropeptides as a serological test, this overview will try to more accurately define the possible roles of specific neuropeptides as prostatic cancer markers in diagnostic and monitoring protocols. The plasma chromogranin A level, in comparison with neuron-specific enolase (NSE), chromogranin B (CBG), pancreastatin, or secretogranin levels, appears to be the most useful neuroendocrine marker for determination of neuroendocrine differentiation of advanced prostatic adenocarcinoma.
Future studies on neuroendocrine should confirm whether neuroendocrine biomarkers, especially the chromogranin family of peptides, can be used as prognostic markers during the course of prostate cancer or for the selection of patients suitable for evaluation of new antineoplastic drugs known to be active against specific and aggressive subpopulations of tumor cells.
前列腺癌与其他实体瘤一样，是一种异质性很强的疾病。超过50%的前列腺恶性肿瘤含有神经内分泌样细胞，这些细胞不能归因于小细胞前列腺癌或类癌样肿瘤，后两者仅占所有前列腺恶性肿瘤的1%-2%。一些研究人员报告称，前列腺癌中神经内分泌分化的组织病理学判定可能具有预后意义，而其他研究人员并未证实这些结果。然而，基于实验数据，神经内分泌样细胞似乎参与了雄激素非依赖性细胞的产生，并且可能成为前列腺癌新治疗策略的靶点。
对有关前列腺癌神经内分泌表型的文献进行综述。本综述总结了关于前列腺癌神经内分泌表型的大部分已积累的实验和临床数据。我们分析了神经内分泌样细胞在前列腺癌进展中的假定功能，并讨论了神经内分泌表型生物标志物作为前列腺癌诊断和预后因素的地位。
在局限性前列腺癌中经常发现神经内分泌样细胞呈局灶性、斑片状和异质性聚集，这可能解释了在疾病的这一阶段，对于神经内分泌组织学模式对临床结局的预测价值存在各种不同的评估。产生可检测到的血浆嗜铬粒蛋白A升高所需的神经内分泌细胞数量尚未确定，但它与嗜铬粒蛋白A阳性神经内分泌（NE）细胞的数量相关。尽管目前将神经肽用作血清学检测存在明显局限性，但本综述将尝试更准确地界定特定神经肽作为前列腺癌标志物在诊断和监测方案中的可能作用。与神经元特异性烯醇化酶（NSE）、嗜铬粒蛋白B（CBG）、胰抑制素或分泌粒蛋白水平相比，血浆嗜铬粒蛋白A水平似乎是确定晚期前列腺腺癌神经内分泌分化最有用的神经内分泌标志物。
未来关于神经内分泌的研究应证实神经内分泌生物标志物，尤其是嗜铬粒蛋白肽家族，是否可在前列腺癌病程中用作预后标志物，或用于选择适合评估已知对特定侵袭性肿瘤细胞亚群有活性的新型抗肿瘤药物的患者。
