Naslov
EXPRESSION OF TUMOR NECROSIS FACTOR-ALPHA (TNF-A) AND VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) IN GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS (GEP- NETS) AND THEIR CORRELATION WITH TUMOR AGGRESSIVENESS

Autori
Cigrovski Berković, Maja ; Ulamec, Monika ; Radulović, Petra ; Čačev, Tamara ; Zjačić-Rotkvić, Vanja ; Krušlin, Božo ; Kapitanović, Sanja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Acta clinica croatica / - , 2010

Skup
21st Ljudevit Jurak international symposium on comparative pathology

Mjesto i datum
Zagreb, Hrvatska, 04.06.2010. - 05.06.2010

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
gastrointestinal neuroendocrine tumors; TNF-alpha; VEGF

Sažetak
Angiogenesis is a crucial step for tumor growth. Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen, known to induce vascular permeability. Its expression is under the influence of proinflammatory cytokines, mainly tumor necrosis factor-alpha (TNF-α). Recent clinical data have proved the correlation between microvessel density and tumor progression with VEGF expression in tumor tissue. As gastroenteropancreatic neuroendocrine tumors (GEP- NETs) are highly vascularized neoplasms with still unknown etiopathogenesis, we investigated the expression of proinfl ammatory cytokine TNF-α and VEGF in 48 GEP-NET tissues, and correlated it with the expression of Ki67. Surgical and biopsy specimens from 46 gastrointestinal neuroendocrine tumors (GI-NETs) and 2 pancreatic neuroendocrine tumors (PETs) were examined for TNF-α and VEGF expression by immunohistochemistry. Of GI-NETs 15 were of foregut (14 gastric and 1 duodenal) and 31 of midgut origin (12 small intestine, 12 appendix and 7 colon). Among tumors, overall 21 had high proliferative index (>2% Ki67 positive tumor cells) and 27 (including 2 PETs) had low proliferative activity. Immunostaining was graded as follows: 0 no positive cells ; 1 ≤25% positive GEP-NET cells ; 2 >25%-50% positive GEP-NET cells ; and 3 ≥50% positive GEP-NET cells. Spearman test was used on correlation of TNF-α and VEGF with Ki67. Results were considered significant at P<0.05. Weakly positive TNF-α staining was detected in one PET, 4 foregut and 12 midgut tumors, while stronger TNF-α expression (2 and 3) existed in 1 foregut and 17 midgut tumors. Overall 13 tumors were negative for TNF-α. Strong cytoplasmic VEGF immunostaining was detected in 30 midgut and 5 foregut GI-NETs and both PETs, while 5 GI-NETs of foregut origin completely lacked VEGF expression. When TNF-α and VEGF expression was correlated with Ki67, there was a statistically signifi cant correlation between TNF-α and Ki67 (P=0.03), and a tendency to statistically signifi cant correlation between VEGF and Ki67 (P=0.09). Our study has demonstrated that neuroendocrine cells are a major source of TNF-α and VEGF, particularly in midgut GI-NETs. This finding suggests that the mentioned cytokine/growth factor are needed to maintain the differentiated state of capillary vessels in these highly vascularized tumors but also, as there was a correlation between the TNF-α and VEGF expression and tumor proliferative activity, that they are important for tumor progression.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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