J Cancer 2014; 5(6):465-471. doi:10.7150/jca.9235

Research Paper

Activation of Angiogenesis Differs Strongly Between Pulmonary Carcinoids and Neuroendocrine Carinomas and Is Crucial for Carcinoid Tumourgenesis

Fabian D. Mairinger1*, Robert F. H. Walter1, 2*, Robert Werner1, Daniel C. Christoph3, Saskia Ting1, Claudia Vollbrecht4, Konstantinos Zarogoulidis5, Haidong Huang6, Qiang Li6, Kurt W. Schmid1, Jeremias Wohlschlaeger1, Paul Zarogoulidis5✉

1. Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany;
2. Ruhrlandklinik, West German Lung Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany;
3. Department of medical Oncology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany;
4. Institute of Pathology, University Hospital Cologne, Cologne, Germany.
5. Pulmonary Department-Oncology Unit, ``G. Papanikolaou`` General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
6. Department of Respiratory Diseases, Changhai Hospital/First Affiliated Hospital of the Second Military Medical University, Shanghai, People's Republic of China, China.
* Authors equally contributed.

Abstract

Background: Lung cancer still remains the leading cause of cancer for men after prostate cancer and breast cancer for women. Angiogenesis is considered a major microenvironment modifier. Material and Methods: Demographic data and study design; The study is based on a collective of twenty representative specimens of each tumour entity (Typical Carcinoid, Atypical Carcinoid, Large-Cell Neuroendocrine Carcinoma , Small Cell Lung Cancer) for mRNA expression analysis. The following methods were performed: RNA Extraction and RNA Integrity Assessment, NanoString CodeSet Design and Expression Quantification, NanoString Data Processing and Statistical Analysis. Results: KDR rendered significant association to aggressiveness of the tumour and decreases with increasing malignancy (p=0.049). A decreased expression of HIF1A and KDR mRNA as associated with a higher risk of tumour invasion in vessels (HIF1A: p=0.034; KDR: p=0.029). FIGF and HIF1A expression levels are significantly associated with progression-free survival (FIGF: p= 0.021; HIF1A: p= 0.049). CRHR2 and FLT4 are stronger expressed in female than in male patients (CRHR2: p=0.024, FLT4: p=0.004). FIGF expression is still significant between LCNEC and SCLC (p=0.023). FLT4 and KDR show highly significant association to one of the analysed groups (FLT4: p=0.001; KDR: p=0.006). Additionally, HIF1A expression differs significantly between these focus cohorts (p=0.018). Conclusion: We should consider for clinical practice application which factors affect most the tumour growth and distal metastasis, thereafter investigate easy to administer drugs with low side effects. Probably a cluster system of therapy should be established where a drug targets simultaneously different pathways of the same origin.

Keywords: lung cancer, HIF1A, FLT4, FIGF, carcinoid, KDR, CRHR2.

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How to cite this article:
Mairinger FD, Walter RFH, Werner R, Christoph DC, Ting S, Vollbrecht C, Zarogoulidis K, Huang H, Li Q, Schmid KW, Wohlschlaeger J, Zarogoulidis P. Activation of Angiogenesis Differs Strongly Between Pulmonary Carcinoids and Neuroendocrine Carinomas and Is Crucial for Carcinoid Tumourgenesis. J Cancer 2014; 5(6):465-471. doi:10.7150/jca.9235. Available from http://www.jcancer.org/v05p0465.htm