Can insulin-like growth factor 1 (IGF-1), IGF-1 receptor connective tissue growth factor and Ki-67 labelling index have a prognostic role in pulmonary carcinoids?

// Georgios A. Kanakis 1 , Lars Grimelius 2 , Dimitrios Papaioannou 3 , Gregory Kaltsas 1 and Apostolos V. Tsolakis 4, 5,6 1 Department of Pathophysiology, Endocrine Unit, University of Athens Medical School, Athens, Greece 2 Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden 3 Department of Pathology, Hygeia Hospital, Athens, Greece 4 Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden 5 Cancer Center Karolinska (CCK), Karolinska University Hospital Solna, Stockholm, Sweden 6 Department of Medical Sciences, Uppsala University, Uppsala, Sweden Correspondence to: Apostolos V. Tsolakis, email: apobtsol@hotmail.com , apostolos.tsolakis@ki.se Keywords: pulmonary carcinoids; IGF-1; CTGF; HIF-1; Ki-67 Received: October 26, 2017      Accepted: February 21, 2018      Published: April 27, 2018 ABSTRACT Introduction : Altered expression of Insulin-like Growth Factor-1 (IGF-1), its receptor (IGF-1R), Connective Tissue Growth Factor (CTGF) and Hypoxia Inducible Factor-1 (HIF-1), has been implicated in tumorigenesis. So far, these factors have not been studied systematically in Pulmonary Carcinoids (PCs). Aims : To examine IGF-1, IGF-1R, CTGF and HIF-1 expression in PCs, and assess their prognostic value over established factors. Materials & Methods : Retrospective study of 121 PCs (104 Typical and 17 Atypical). The expression of growth factors was studied immunohistochemically and tumors were considered positive if immunoreactivity appeared in >50% of cells. Results : All studied parameters were expressed in the majority of tumors (IGF-1, IGF-1R, CTGF and HIF-1, in 78.5%, 67%, 72% and 78%, respectively). Their expression tended to be more frequent in TCs and in tumors with Ki-67≤2% (significant only for HIF-1; 82 vs. 53%; p=0.023 and 83 vs. 63%; p=0.025 respectively). CTGF was the only factor correlated with more extensive disease (larger size; presence of lymph node and distant metastases). According to logistic regression analysis, only advanced age, Ki-67≥3.4% and lymph node involvement could predict the development of distant metastases. Conclusions : IGF-1, IGF-1R, CTGF and HIF-1 are avidly expressed in PCs; however, their presence did not appear to be of statistically significant value over established prognostic factors.