The matrix metalloproteinases (MMPs) are a family of zinc-containing 
endopeptidases that are able to degrade the extracellular matrix and allow 
angiogenesis 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 
collagenase 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 
sections of pituitary tumors. Invasive macroprolactinomas (n = 11) were 
significantly more likely to express MMP-9 than noninvasive macroprolactinomas 
(n = 8) (P = 0.003). Invasive macroprolactinomas showed higher-density MMP-9 
staining than noninvasive tumors (P < 0.05). MMP-9 expression did not differ 
between noninvasive tumors and normal pituitary gland, or between different 
sized prolactinomas. MMP-9 expression was related to aggressive tumor behavior. 
It was higher in invasive macroprolactinomas (P = 0.003) when compared with 
noninvasive macroprolactinomas or the normal anterior pituitary gland. In 
addition, although there was no difference in whether MMP-9 was present or not 
when nonfunctioning adenomas that recurred were compared with those that did 
not, samples of recurrent tumor at the second presentation were more likely to 
express MMP-9 (P = 0.01). Pituitary carcinomas were significantly more likely to 
be MMP-9 positive compared with normal anterior pituitary gland (P = 0.05), but 
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 carcinoma. The mechanisms whereby 
MMP-9 expression influences tumor recurrence and invasiveness, and its 
association with angiogenesis, remains to be elucidated. However, these 
observations suggest that a future potential therapeutic strategy for some 
pituitary tumors may be administration of a synthetic MMP-9 inhibitor.