Oncotarget

Research Papers: Pathology:

Identification of deregulation of apoptosis and cell cycle in neuroendocrine tumors of the lung via NanoString nCounter expression analysis

Robert Fred Henry Walter _, Robert Werner, Saskia Ting, Claudia Vollbrecht, Dirk Theegarten, Daniel Christian Christoph, Kurt Werner Schmid, Jeremias Wohlschlaeger and Fabian Dominik Mairinger

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Oncotarget. 2015; 6:24690-24698. https://doi.org/10.18632/oncotarget.3992

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Abstract

Robert Fred Henry Walter1,2, Robert Werner2, Saskia Ting2, Claudia Vollbrecht3, Dirk Theegarten2, Daniel Christian Christoph4, Kurt Werner Schmid2, Jeremias Wohlschlaeger2 and Fabian Dominik Mairinger2

1 Ruhrlandklinik, West German Lung Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

2 Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

3 Institute of Pathology, University Hospital Cologne, Cologne, Germany

4 Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

Correspondence to:

Robert Fred Henry Walter, email:

Keywords: small-cell lung cancer, large-cell neuroendocrine lung cancer, carcinoids, apoptosis, NanoString nCounter

Received: March 11, 2015 Accepted: April 15, 2015 Published: May 04, 2015

Abstract

Background: Neuroendocrine tumors of the lung comprise typical (TC) and atypical carcinoids (AC), large-cell neuroendocrine cancer (LCNEC) and small-cell lung cancer (SCLC). Cell cycle and apoptosis are key pathways of multicellular homeostasis and deregulation of these pathways is associated with cancerogenesis.

Materials and Methods: Sixty representative FFPE-specimens (16 TC, 13 AC, 16 LCNEC and 15 SCLC) were used for mRNA expression analysis using the NanoString technique. Eight genes related to apoptosis and ten genes regulating key points of cell cycle were investigated.

Results: ASCL1, BCL2, CASP8, CCNE1, CDK1, CDK2, CDKN1A and CDKN2A showed lower expression in carcinoids compared to carcinomas. In contrast, CCNE1 and CDK6 showed elevated expression in carcinoids compared to carcinomas. The calculated BCL2/BAX ratio showed increasing values from TC to SCLC.

Between SCLC and LCNEC CDK2, CDKN1B, CDKN2A and PNN expression was significantly different with higher expression in SCLC.

Conclusion: Carcinoids have increased CDK4/6 and CCND1 expression controlling RB1 phosphorylation via this signaling cascade. CDK2 and CCNE1 were increased in carcinomas showing that these use the opposite way to control RB1. BAX and BCL2 are antagonists in regulating apoptosis. BCL2 expression increased over BAX expression with increasing malignancy of the tumor from TC to SCLC.


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