Endothelial expression of endocan is strongly associated with tumor progression in pituitary adenoma

Although benign, pituitary adenomas frequently invade adjacent sinuses or recur after first surgery. To date, there is no histological marker predictive of recurrence. Angiogenic factors are candidate markers. Endocan is a proteoglycan secreted by endothelial cells, associated with an aggressive behavior in several tumor types. Endocan expression was investigated by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) in 18 normal post-mortem pituitaries and in 107 patients operated for a pituitary adenoma (with a follow-up of at least 8 years after surgery). In normal pituitaries, endocan was never observed in vessels but was detected in isolated endocrine cells. In adenoma tissue, we found a strong association between endocan immunoreactivity in endothelial cells and progression (P = 0.0009), as well as tumor size (P = 0.0012), raised mitotic count (P = 0.02) and p53 expression (P = 0.032). Morphometric analysis of the microvessels showed that the mean vessel area was significantly higher in the subgroup of tumors with an endothelial expression of endocan (P = 0.028), coherent with the neoangiogenesis process occurring in the pituitary. The immunolabeling of endocan in endothelial cells may therefore appear to be a relevant marker of aggressive behavior in pituitary tumors.