Research Papers:

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, Lars Grimelius, Dimitrios Papaioannou, Gregory Kaltsas and Apostolos V. Tsolakis _

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Oncotarget. 2018; 9:22653-22664. https://doi.org/10.18632/oncotarget.25203

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Georgios A. Kanakis1, Lars Grimelius2, Dimitrios Papaioannou3, Gregory Kaltsas1 and Apostolos V. Tsolakis4,5,6

1Department of Pathophysiology, Endocrine Unit, University of Athens Medical School, Athens, Greece

2Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

3Department of Pathology, Hygeia Hospital, Athens, Greece

4Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden

5Cancer Center Karolinska (CCK), Karolinska University Hospital Solna, Stockholm, Sweden

6Department of Medical Sciences, Uppsala University, Uppsala, Sweden

Correspondence to:

Apostolos V. Tsolakis, email: [email protected], [email protected]

Keywords: pulmonary carcinoids; IGF-1; CTGF; HIF-1; Ki-67

Received: October 26, 2017     Accepted: February 21, 2018     Published: April 27, 2018


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.

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