Role of Ki-67 Proliferation Index in the Assessment of Patients with Neuroendocrine Neoplasias Regarding the Stage of Disease
Role of Ki-67 Proliferation Index in the Assessment of Patients with Neuroendocrine Neoplasias Regarding the Stage of Disease
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DOI：
10.1007/s00268-014-2451-0
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发表时间：
2014-06-01
影响因子：
2.6
通讯作者：
Frilling, A.
中科院分区：
文献类型：
--
作者：
Miller, H. C.;Drymousis, P.;Frilling, A.
胃肠胰（GEP）系统的神经内分泌肿瘤（NEN）经常出现转移性沉积。增殖标志物Ki-67用于诊断和评估疾病的预后。我们研究的目的是评估Ki-67%在临床实践中评估NEN患者疾病分期方面的有用性。此外，我们还对不同疾病部位的Ki-67水平进行了比较分析。这项回顾性研究包括2010年至2012年在我中心转诊的GEP NEN患者。NEN诊断通过标准组织病理学证实。使用自动化Leica免疫组织化学仪在石蜡包埋切片上进行Ki-67免疫组织化学。根据欧洲神经内分泌肿瘤学会的建议进行NEN分级（低级别[G1]至中等级别[G2]，高分化至中等分化的神经内分泌肿瘤;高级别[G3]，中等分化至低分化的神经内分泌肿瘤）。肿瘤分期与分级结果相关。在一个亚组的情况下，Ki-67水平在不同部位的疾病进行了比较分析。161例GEP NEN患者纳入本研究。在46.1%（53/115）的G1肿瘤、77.8%（28/36）的G2肿瘤和100%（10/10）的G3肿瘤中观察到转移性疾病（p = 0.0002）。当根据原发肿瘤部位分层时，42.9%（36/84）的胰腺NEN患者和91.9%（34/37）的小肠原发性NEN患者记录了转移性疾病。IV期转移性疾病分别存在于27.8%（32/115）和72.2%（26/36）的G1和G2肿瘤中，并且存在于90%（9/10）的G3肿瘤中。在转移部位以及原发肿瘤部位的病例子集的Ki-67指数评估显示35.3%的病例存在差异。在7/9例（77.8%）肝转移患者中，肝病灶中的Ki-67%高于原发肿瘤。根据原发肿瘤部位，预期低Ki-67%的肿瘤也会发生转移，尽管它们被认为侵袭性较低。不同的疾病部位可能表达不同的Ki-67水平。
Neuroendocrine neoplasias (NEN) of the gastroenteropancreatic (GEP) system frequently present with metastatic deposits. The proliferation marker Ki-67 is used for diagnosis and to assess the prognosis of disease. The aim of our study was to evaluate the usefulness of Ki-67 % in the assessment of NEN patients with regard to their disease stage in clinical practice. Additionally, a comparative analysis of Ki-67 levels among different sites of disease was performed.This retrospective study included patients with GEP NEN referred to our center from 2010 to 2012. The NEN diagnosis was confirmed by standard histopathology. Ki-67 immunohistochemistry was done on paraffin-embedded sections using an automated Leica immunohistochemistry machine. NEN grading was carried out according to European Neuroendocrine Tumor Society recommendations (low grade [G1] to intermediate grade [G2], well to moderately differentiated neuroendocrine neoplasms; high-grade [G3], moderately to poorly differentiated neuroendocrine neoplasms). Results of tumor staging and grading were correlated. In a subgroup of cases, comparative analysis of Ki-67 levels in different sites of disease was carried out.One hundred sixty-one GEP NEN patients were included in the study. Metastatic disease was seen in 46.1 % (53/115) of G1 tumors, 77.8 % (28/36) of G2 tumors, and 100 % of (10/10) G3 tumors (p = 0.0002). When stratified according to primary tumor site, metastatic disease was documented in 42.9 % (36/84) of patients with pancreatic NEN and in 91.9 % (34/37) of those with small intestinal primary. Stage IV metastatic disease was present in 27.8 % (32/115) and 72.2 % (26/36) of the G1 and G2 tumors, respectively, and in 90 % (9/10) of the G3 tumors. Assessment of the Ki-67 index for a subset of cases at metastatic sites as well as the primary tumor site showed discrepancies in 35.3 % cases. In 7/9 (77.8 %) patients with liver metastases, Ki-67 % was higher in the liver lesions than in the primary tumor.Patients with GEP NEN exhibiting a high Ki-67 proliferation index present with metastatic disease in the vast majority of cases. Depending upon the primary tumor site, metastases are to be expected also in tumors with low Ki-67 %, although they are considered less aggressive. Different disease sites may express heterogeneous Ki-67 levels.