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


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

Fabian D Mairinger et al. J Cancer.


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: CRHR2.; FIGF; FLT4; HIF1A; KDR; carcinoid; lung cancer.

Conflict of interest statement

Conflict of Interest: All authors disclose any affiliations that are considered to be relevant and important with any organization that to our knowledge has any direct interest in the subject matter discussed.


Figure 1
Figure 1
TC; typical carcinoid, AC; atypical carcinoid, sclc; small cell lung cancer, LCLC; large-cell neuroendocrine carcinoma, FLT4; Fms-related tyrosine kinase 4, FIGF; C-fos-induced growth factor.
Figure 2
Figure 2
FIGF; C-fos-induced growth factor, HIF1A; Hypoxia-inducible factor 1-alpha.
Figure 3
Figure 3
CRHR2; Corticotropin releasing hormone receptor 2.
Figure 4
Figure 4
HIF1A; Hypoxia-inducible factor 1-alpha, KDR; Kinase insert domain receptor.

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    1. Eramo A. et al. Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ. 2008;15(3):504–14. - PubMed
    1. Jett J.R. and Midthun D.E. Screening for lung cancer: current status and future directions: Thomas A. Neff lecture. Chest. 2004;125(5 Suppl):158–62. - PubMed
    1. Mallick R, MicroRNAs and lung cancer: Biology and applications in diagnosis and prognosis. J Carcinog. 2010. 9. - PMC - PubMed
    1. Rekhtman N. Neuroendocrine tumors of the lung: an update. Arch Pathol Lab Med. 2010;134(11):1628–38. - PubMed
    1. Takei H. et al. Large cell neuroendocrine carcinoma of the lung: a clinicopathologic study of eighty-seven cases. J Thorac Cardiovasc Surg. 2002;124(2):285–92. - PubMed