Data on the dural invasiveness of pituitary adenomas have been correlated to the 
expression of matrix metalloproteinases (e.g. MMP-9). Serine proteases have not 
yet been investigated in human pituitary adenomas. In this study, 
paraffin-embedded material from 84 human pituitary adenomas (acromegaly n=18, 
Cushing's disease n=21, prolactinoma n=18, thyroid-stimulating hormone-secreting 
adenoma n=1, nonsecreting adenoma n=26) and 9 nontumourous anterior pituitary 
lobes (obtained from patients with prostate cancer) was immunohistochemically 
analysed for expression of MMP-2, MMP-9, tissue inhibitor of 
metalloproteinases-2 (TIMP-2), urokinase-type plasminogen activator (uPA), uPA 
receptor (uPAR), tissue-type plasminogen activator (tPA), plasminogen activator 
inhibitor-1 (PAI-1), and interleukin-6 (IL-6). Cavernous sinus invasion was 
determined by assessment of preoperative magnetic resonance imaging and 
intraoperative inspection (invasive n=50, noninvasive n=34). In pituitary 
adenomas, reactions were positive (diffuse expression) to MMP-2 (74% of cases), 
MMP-9 (49%), TIMP-2 (88%), uPA (89%), uPAR (90%), tPA (69%), and PAI-1 (87%). A 
weak expression of IL-6 was found in 12% of the adenomas. All reactions were 
positive (focal expression) in every sample of anterior lobe tissue, except for 
uPA (negative in 3 out of 9 cases), and IL-6 (faintly positive in 5 out of 8 
cases). Adenomas showed remarkably greater expression of uPA than anterior lobe 
tissue (Chi-square P<0.05). Nonsecreting adenomas exhibited a stronger tendency 
towards overexpression of uPA in invasive tumours when compared to noninvasive 
adenomas (Chi-square P=0.053). We found no correlation of MMP-9 expression and 
tumour invasion. TIMP-2 was overexpressed in noninvasive as compared to invasive 
adenomas (Chi-square P<0.05). The interrelationship between MMPs and serine 
proteinases in pituitary adenomas remains to be elucidated. From our data, a 
correlation between IL-6 and an activation of MMP-9 cannot be proven. The 
uPA-system may, however, play a role in dural invasion of pituitary adenomas.