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

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.