Department of Internal MedicineSector of Endocrinology, Erasmus MC, 's Gravendijkwal 230, Room D-430, 3015 CE Rotterdam, The Netherlands Department of SurgeryErasmus MC, Rotterdam, The Netherlands Department of PathologyErasmus MC, Rotterdam, and Reinier de Graaf Hospital, Delft, The Netherlands.
Endocr Connect. 2013 Dec 1;2(4):172-7. doi: 10.1530/EC-13-0052. Print 2013.
Chromogranin A (CgA) and the Ki-67 proliferation index are considered as important biochemical and pathological markers for clinical behaviour of gastroenteropancreatic neuroendocrine tumors (GEP NETs), respectively. The IGF system has been suggested as an important regulator of GEP NET proliferation and differentiation. A possible relationship between serum CgA (sCgA), Ki-67 proliferation index, and expression of IGF-related genes in patients with GEP NETs has not been demonstrated yet. This study investigates the relationship between sCgA, the Ki-67 proliferation index, and the expression of IGF-related genes in GEP NET tissues and their relation with 5-year survival. Tumor and blood samples from 22 GEP NET patients were studied.
TUMORAL MRNA EXPRESSION OF IGF-RELATED GENES (IGFS: IGF1, IGF2; IGF receptors: IGF1R, IGF2R; insulin receptors: subtype A (IR-A) and B (IR-B); IGF-binding proteins (IGFBPs): IGFBP1, IGFBP2, IGFBP3, and IGFBP6) was measured using quantitative RT-PCR. Ki-67 proliferation index was determined using immunohistochemistry. sCgA was measured with ELISA. Five-year survival in patients with nonelevated sCgA (n=11) was 91 vs 46% in patients with elevated sCgA (n=11) (P=0.006). IR-A mRNA expression was significantly higher in tumors obtained from patients with elevated sCgA than in those from patients with nonelevated sCgA (6.42±2.08 vs 2.60±0.40; P=0.04). This data suggests that sCgA correlates well with 5-year survival of GEP NET patients, and that IR-A mRNA expression correlates well with tumor mass in GEP NET patients.
嗜铬粒蛋白 A（CgA）和 Ki-67 增殖指数分别被认为是胃肠胰神经内分泌肿瘤（GEP NET）临床行为的重要生化和病理标志物。IGF 系统被认为是 GEP NET 增殖和分化的重要调节因子。GEP NET 患者血清 CgA（sCgA）、Ki-67 增殖指数与 IGF 相关基因表达之间的可能关系尚未得到证实。本研究旨在探讨 GEP NET 组织中 sCgA、Ki-67 增殖指数与 IGF 相关基因表达之间的关系及其与 5 年生存率的关系。研究了 22 例 GEP NET 患者的肿瘤和血液样本。
采用定量 RT-PCR 测定 IGF 相关基因（IGFS：IGF1、IGF2；IGF 受体：IGF1R、IGF2R；胰岛素受体亚型 A（IR-A）和 B（IR-B）；IGF 结合蛋白（IGFBPs）：IGFBP1、IGFBP2、IGFBP3 和 IGFBP6）的肿瘤 mRNA 表达。采用免疫组织化学法测定 Ki-67 增殖指数。采用 ELISA 法测定 sCgA。无升高 sCgA（n=11）的患者 5 年生存率为 91%，升高 sCgA（n=11）的患者为 46%（P=0.006）。与无升高 sCgA 的患者相比，升高 sCgA 的患者肿瘤中 IR-A mRNA 表达明显升高（6.42±2.08 vs 2.60±0.40；P=0.04）。该数据表明，sCgA 与 GEP NET 患者的 5 年生存率密切相关，而 IR-A mRNA 表达与 GEP NET 患者的肿瘤负荷密切相关。
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