IGF-IEc expression is increased in secondary compared to primary foci in neuroendocrine neoplasms
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Krystallenia I. Alexandraki1, Anastassios Philippou2, Georgios Boutzios1, Irini Theohari3, Michael Koutsilieris2, Ioanna Kassiani Delladetsima3 and Gregory A. Kaltsas1
1Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
2Department of Experimental Physiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
3First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
Krystallenia I. Alexandraki, email: [email protected]
Keywords: neuroendocrine neoplasms, IGF-IEc, IGF-I, Ki-67, metastasis
Received: November 01, 2016 Accepted: August 07, 2017 Published: September 08, 2017
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.
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