Department of Clinical Chemistry, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, PO Box 90203, 1006 BE Amsterdam, The Netherlands.
Eur J Cancer. 2012 Mar;48(5):662-71. doi: 10.1016/j.ejca.2011.08.012. Epub 2011 Sep 22.
Chromogranin A (CgA) is the most important tumour marker for well-differentiated neuroendocrine tumours (NET) and neuron specific enolase (NSE) for poorly differentiated neuroendocrine carcinoma (NEC). This study investigated whether the markers progastrin-releasing peptide (proGRP) and cytokeratin fragments (CKfr) CK8, CK18 and CK19 (MonoTotal) can be of additional value to the histological classification and help predict survival in these patients.
CgA, NSE, proGRP and CKfr were measured in 242 patients with grade 1 NET (G1NET), 38 with grade 2 NET (G2NET), 42 with large cell NEC (LCNEC), 251 with small cell NEC (SCNEC) and in 282 healthy persons. Results were compared with tumour characteristics and survival by means of Receiver Operating Characteristics (ROC) curves and Cox regression analyses.
The largest area under the ROC curve was for CgA (0.86, 0.91 and 0.90, respectively) when comparing patients with G1NET, G2NET and LCNEC with healthy persons. ProGRP showed the highest sensitivity (73%) at 95% specificity in patients with SCNEC. In a multivariate survival analysis, only CKfr was associated with survival (P<0.0001) for patients with well-differentiated NET (G1NET and G2NET). For patients with poorly differentiated NEC, both CKfr and NSE were associated with survival (P<0.0001 and P=0.003, respectively).
Within all histological groups a combination of tumour markers proved to be more informative as diagnostic and prognostic marker than each marker alone. In patients with well-differentiated NET and LCNEC we recommend the use of CgA and CKfr, whilst in patients with SCNEC, proGRP and CKfr are preferred.
嗜铬粒蛋白 A（CgA）是分化良好的神经内分泌肿瘤（NET）最重要的肿瘤标志物，神经元特异性烯醇化酶（NSE）是分化差的神经内分泌癌（NEC）的标志物。本研究旨在探讨胃泌素释放肽前体（proGRP）和细胞角蛋白片段（CKfr）CK8、CK18 和 CK19（MonoTotal）是否具有额外的价值，以辅助组织学分类，并预测这些患者的生存情况。
在 242 例 1 级 NET（G1NET）、38 例 2 级 NET（G2NET）、42 例大细胞 NEC（LCNEC）、251 例小细胞 NEC（SCNEC）和 282 例健康人群中，测量了 CgA、NSE、proGRP 和 CKfr。通过接收者操作特征（ROC）曲线和 Cox 回归分析比较了这些标志物与肿瘤特征和生存情况的相关性。
比较 G1NET、G2NET 和 LCNEC 患者与健康人群时，CgA 的 ROC 曲线下面积最大（分别为 0.86、0.91 和 0.90）。在 SCNEC 患者中，proGRP 的灵敏度最高（73%），特异性为 95%。在多变量生存分析中，只有 CKfr 与分化良好的 NET（G1NET 和 G2NET）患者的生存情况相关（P<0.0001）。对于分化差的 NEC 患者，CKfr 和 NSE 均与生存相关（P<0.0001 和 P=0.003）。
在所有组织学分组中，肿瘤标志物的联合检测比单一标志物更具有诊断和预后价值。对于分化良好的 NET 和 LCNEC 患者，我们建议使用 CgA 和 CKfr，而对于 SCNEC 患者，proGRP 和 CKfr 则是首选。
