Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan, 20122, Italy.
Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Endocrine. 2017 Nov;58(2):360-367. doi: 10.1007/s12020-017-1249-x. Epub 2017 Feb 17.
Small-intestine neuroendocrine neoplasms are heterogeneous neoplasms arising from endocrine cells of the intestinal mucosa. Ki-67 is the main determinant of prognosis in neuroendocrine neoplasms. However, the search for new prognostic makers represents a key point with regard to small-intestine neuroendocrine neoplasms. The oncofetal protein IMP3 plays a role in cell growth and its expression has a prognostic value in lung neoplasms.
From January 1998 to August 2015, all the consecutive small-intestine neuroendocrine neoplasms patients suitable for surgery were included: 51 patients (32 males, median age 68 years) had small-intestine neuroendocrine neoplasms classified according to the WHO 2010 classification. In all the cases IMP3 expression was evaluated on primary tumors and, when available, on nodal and distant metastases. The medical records and pathological slides of these patients were used to determine the clinical characteristics, pathological diagnoses, and outcome information.
The overall 5-year and 10-year survival rate were 53.9 and 42% respectively. At Cox proportional hazards regression grading was the major factor influencing both OS and progression-free survival at univariate (p = 0.0002 and 0.0051, respectively) and multivariate analysis (p = 0.0004 and 0.0043, respectively). Also IMP3 expression at the nodal metastases resulted a factor significantly associated with progression-free survival at both univariate (p = 0.0066) and multivariate analysis (p = 0.0059, HR 3.58). IMP3 expression did not correlate with the Ki-67 (p = n.s.).
In this study, IMP3 at the nodal site resulted to be associated with low progression-free survival in small-intestine neuroendocrine neoplasms, independently of the Ki-67 index. We suggest that the integration of IMP3 and Ki-67 would help better stratify the risk of progression in small-intestine neuroendocrine neoplasms.
小肠神经内分泌肿瘤是起源于肠黏膜内分泌细胞的异质性肿瘤。Ki-67 是神经内分泌肿瘤预后的主要决定因素。然而，寻找新的预后标志物是小肠神经内分泌肿瘤的一个关键点。癌胚蛋白 IMP3 在细胞生长中起作用，其表达在肺癌中具有预后价值。
从 1998 年 1 月至 2015 年 8 月，所有适合手术的连续小肠神经内分泌肿瘤患者均被纳入研究：51 例患者（男 32 例，中位年龄 68 岁）根据 2010 年 WHO 分类标准进行小肠神经内分泌肿瘤分类。所有病例均在原发肿瘤及淋巴结和远处转移灶中评估 IMP3 表达。使用这些患者的病历和病理切片来确定临床特征、病理诊断和结果信息。
总体 5 年和 10 年生存率分别为 53.9%和 42%。在 Cox 比例风险回归分析中，分级是影响 OS 和无进展生存期的主要因素（单因素分析时分别为 p=0.0002 和 0.0051，多因素分析时分别为 p=0.0004 和 0.0043）。在淋巴结转移灶中，IMP3 的表达也是与无进展生存期显著相关的因素（单因素分析时 p=0.0066，多因素分析时 p=0.0059，HR 3.58）。IMP3 的表达与 Ki-67 无关（p=ns）。
在本研究中，淋巴结部位的 IMP3 与小肠神经内分泌肿瘤的无进展生存期降低相关，与 Ki-67 指数无关。我们建议，IMP3 和 Ki-67 的整合将有助于更好地分层小肠神经内分泌肿瘤的进展风险。
