Circulating levels of angiogenic cytokines can predict tumour progression and prognosis in neuroendocrine carcinomas.
OBJECTIVE
The growth behaviour of well-differentiated neuroendocrine carcinomas of the gastro-entero-pancreatic system varies greatly and parameters predicting their prognosis are lacking. The aim of our study was to investigate whether tumour growth could be correlated with the release of proangiogenic factors into the circulation.


METHODS
Circulating vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), basic fibroblast growth factor (bFGF) and angiogenin were measured in 38 patients with advanced neuroendocrine carcinomas and compared to healthy age-matched controls. In 20 patients, angiogenic cytokine levels were measured at consecutive time points and correlated to tumour progression as assessed by abdominal CT scan, MRI and chromogranin A levels.


RESULTS
VEGF levels were elevated in patients compared to controls (P < 0.002) and clearly associated with tumour progression (P < 0.005). Angiogenin levels were significantly higher in patients than in controls (P < 0.003), while high IL-8 levels were predictive of shorter survival. Angiogenin and bFGF levels were correlated neither with tumour growth nor with patient survival.


CONCLUSIONS
VEGF and IL-8 are associated with tumour progression and might qualify as markers of prognosis and therapy control in patients with neuroendocrine carcinomas. Our results support the notion that specific anti-angiogenic therapies should be evaluated in neuroendocrine carcinoma patients.
Pavel
Marianne E
ME
Department of Medicine I, University Hospital Erlangen-Nuernberg, Ulmensweg 18, 91054 Erlangen, Germany. marianne.pavel@med1.uni-erlangen.de
Hassler
Gerda
G
Baum
Ulrich
U
Hahn
Eckhart G
EG
Lohmann
Tobias
T
Schuppan
Detlef
D
D000328:Adult; D000368:Aged; D042501:Angiogenic Proteins / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D007414:Intestinal Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000097:blood* / Q000401:mortality / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology; D011237:Predictive Value of Tests; D012259:Ribonuclease, Pancreatic / Q000097:blood; D013274:Stomach Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D042501:Angiogenic Proteins; D014408:Biomarkers, Tumor; D016209:Interleukin-8; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C046366:angiogenin; D012259:Ribonuclease, Pancreatic