Grillo Federica, Albertelli Manuela, Brisigotti Maria Pia, Borra Tiziana, Boschetti Mara, Fiocca Roberto, Ferone Diego, Mastracci Luca
Neuroendocrinology. 2016;103(5):452-9. doi: 10.1159/000439434. Epub 2015 Aug 25.
BACKGROUND/AIM: The neuroendocrine tumor (NET) proliferation-based grading system (ENETS/WHO) for gastroenteropancreatic (GEP) tumors has proved reliable for prognostic stratification. To date, concerns exist regarding Ki-67 heterogeneity within the tumor and little is known on whether grade varies between primary and secondary sites. As tumor heterogeneity may have a significant impact on clinical management, our aim was to retrospectively evaluate Ki-67 on a series of GEP NETs in order to establish whether there is variability in different samples of the same lesion or between primary and metastatic disease (local/distant, synchronous/metachronous).
Sixty patients with multiple samples of tumor were accrued from a total of 338 GEP NETs; 44 of them also had tissue from local/distant metastases and a further 5 had multiple metastatic foci from unknown primary tumors. Immunohistochemistry for Ki-67 was performed on all paraffin blocks from both primary and metastatic tumors.
Intratumor Ki-67 heterogeneity sufficient to change grade at first diagnosis was seen in 3/60 cases (5%). Out of 49 patients with primary NETs and/or multiple metastases, discrepancy in grade between sites was identified in 19 (39%) cases and in particular in 11/47 (23%) and in 10/12 (83%) patients with synchronous and metachronous metastases, respectively (p = 0.0002). Change in grade was more frequent in distant compared to locoregional metastases (p = 0.024) and in particular in distant sites other than the liver (p = 0.006).
NETs show frequent differences in grade between primary sites and their synchronous/metachronous metastases; assessment of Ki-67 at all sites may prove to be significant for patient management.
背景/目的：胃肠胰（GEP）肿瘤基于神经内分泌肿瘤（NET）增殖的分级系统（ENETS/WHO）已被证明在预后分层方面是可靠的。迄今为止，人们对肿瘤内Ki-67的异质性存在担忧，并且对于原发部位和继发部位之间的分级是否不同知之甚少。由于肿瘤异质性可能对临床管理产生重大影响，我们的目的是回顾性评估一系列GEP NETs中的Ki-67，以确定同一病变的不同样本之间或原发疾病与转移性疾病（局部/远处、同时性/异时性）之间是否存在差异。
从总共338例GEP NETs中收集了60例有多个肿瘤样本的患者；其中44例还拥有局部/远处转移灶的组织，另有5例有来自未知原发肿瘤的多个转移灶。对原发肿瘤和转移肿瘤的所有石蜡块进行Ki-67免疫组织化学检测。
在60例病例中有3例（5%）出现了足以在初次诊断时改变分级的肿瘤内Ki-67异质性。在49例有原发性NETs和/或多个转移灶的患者中，19例（39%）病例的不同部位之间存在分级差异，特别是在同时性转移和异时性转移的患者中分别有11/47（23%）和10/12（83%）出现差异（p = 0.0002）。与局部区域转移相比，远处转移的分级变化更频繁（p = 0.024），特别是在肝脏以外的远处部位（p = 0.006）。
NETs在原发部位与其同时性/异时性转移灶之间的分级经常存在差异；对所有部位的Ki-67进行评估可能对患者管理具有重要意义。
