IGF-IEc expression is increased in secondary compared to primary foci in neuroendocrine neoplasms

// Krystallenia I. Alexandraki 1 , Anastassios Philippou 2 , Georgios Boutzios 1 , Irini Theohari 3 , Michael Koutsilieris 2 , Ioanna Kassiani Delladetsima 3 and Gregory A. Kaltsas 1 1 Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece 2 Department of Experimental Physiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece 3 First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece Correspondence to: Krystallenia I. Alexandraki, email: alexandrakik@gmail.com Keywords: neuroendocrine neoplasms, IGF-IEc, IGF-I, Ki-67, metastasis Received: November 01, 2016      Accepted: August 07, 2017      Published: September 08, 2017 ABSTRACT 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.