Alexandraki Krystallenia I, Philippou Anastassios, Boutzios Georgios, Theohari Irini, Koutsilieris Michael, Delladetsima Ioanna Kassiani, Kaltsas Gregory A
Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Department of Experimental Physiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Oncotarget. 2017 Sep 8;8(45):79003-79011. doi: 10.18632/oncotarget.20743. eCollection 2017 Oct 3.
Different Insulin-like growth factor-I (IGF-I) mRNA transcripts are produced by alternative splicing and particularly the IGF-IEc isoform has been implicated in the development and/or progression of various types of cancer. In the present study, we examined the potential role of IGF-IEc expression as a new immunohistochemical marker of aggressiveness in neuroendocrine neoplasms (NENs). We utilized immunohistochemical analysis in tissue specimens of 47 patients with NENs, to evaluate the expression of IGF-IEc (%) and Ki-67 proliferation index (%). Specimens from patients with tumors of different tissue origin, of either primary or metastatic lesions and of different grade were examined. Cytoplasmic IGF-IEc staining was found in 23 specimens of NENs or NECs: 10 pancreatic, 4 small bowel, 3 gastric, 1 lung, 1 uterine and 4 poorly differentiated of unknown primary origin. Ki-67 and IGF-IEc expression was positively correlated in all the samples studied (r=0.31, p=0.03). IGF-1Ec expression was more prevalent in specimens originating from metastatic foci with high Ki-67 compared to primary sites with low Ki-67 expression (p=0.036). These findings suggest a possible role of IGF-IEc in NEN tumorigenesis and progression to metastases that could be used as an additional new marker of a more aggressive behavior and a potential drugable target.
不同的胰岛素样生长因子-I（IGF-I）mRNA转录本通过可变剪接产生，尤其是IGF-IEc亚型与多种癌症的发生和/或进展有关。在本研究中，我们检测了IGF-IEc表达作为神经内分泌肿瘤（NENs）侵袭性新免疫组织化学标志物的潜在作用。我们对47例NENs患者的组织标本进行免疫组织化学分析，以评估IGF-IEc的表达（%）和Ki-67增殖指数（%）。检查了来自不同组织来源、原发性或转移性病变以及不同分级肿瘤患者的标本。在23例NENs或神经内分泌癌（NECs）标本中发现了细胞质IGF-IEc染色：10例胰腺、4例小肠、3例胃、1例肺、1例子宫和4例原发灶不明的低分化肿瘤。在所有研究样本中，Ki-67和IGF-IEc表达呈正相关（r=0.31，p=0.03）。与Ki-67表达低的原发部位相比，IGF-1Ec表达在Ki-67高的转移灶标本中更普遍（p=0.036）。这些发现表明IGF-IEc在NEN肿瘤发生和转移进展中可能起作用，可作为更具侵袭性的行为的额外新标志物和潜在的可药物作用靶点。
