Role of matrix metalloproteinase 9 in pituitary tumor behavior

The matrix metalloproteinases (MMPs) are a family of zinc-containing endope ptidases that are able to degrade the extracellular matrix and allow angiog enesis and tumor invasion. The vast majority of pituitary tumors are benign and do not metastasize to distant sites, although they may invade locally. The aim of this study was to determine whether expression of the collagena se MMP-9 may play a role in allowing angiogenesis and invasion by different pituitary tumor types. Tumor expression of MMP-9 was investigated using a monoclonal antibody on a series of well-characterized paraffin-embedded sec tions of pituitary tumors. Invasive macroprolactinomas (n = 11) were significantly more likely to expr ess MMP-9 than noninvasive macroprolactinomas (n = 8) (P = 0.003). Invasive macroprolactinomas showed higher-density MMP-9 staining than noninvasive t umors (P < 0.05). MMP-9 expression did not differ between noninvasive tumor s and normal pituitary gland, or between different sized prolactinomas. MMP -9 expression was related to aggressive tumor behavior. It was higher in in vasive macroprolactinomas (P = 0.003) when compared with noninvasive macrop rolactinomas or the normal anterior pituitary gland. In addition, although there was no difference in whether MMP-9 was present or not when nonfunctio ning adenomas that recurred were compared with those that did not, samples of recurrent tumor at the second presentation were more likely to express M MP-9 (P = 0.01). Pituitary carcinomas were significantly more likely to be MMP-9 positive compared with normal anterior pituitary gland (P = 0.05), bu t there was no difference from invasive adenomas. Angiogenesis assessed by vascular density was related to MMP-9 expression (P < 0.05). In summary, we have shown the presence of MMP-9 expression in some invasive and recurrent pituitary adenomas, and in the majority of pituitary carcino ma. The mechanisms whereby MMP-9 expression influences tumor recurrence and invasiveness, and its association with angiogenesis, remains to be elucida ted. However, these observations suggest that a future potential therapeuti c strategy for some pituitary tumors may be administration of a synthetic M MP-9 inhibitor.