BACKGROUND & OBJECTIVE: Usually pituitary adenomas are histological benign and 
grow slowly, but a proportion of them will become locally aggressive, and 
develop into invasive pituitary adenomas. The reasons for these differences in 
tumor behavior are poorly understood. Pituitary adenomas are abounding blood 
vessels. Angiogenesis and tumor invasion both require degradation of the 
extracellular matrix components to allow cell migration. The matrix 
metalloproteinases (MMPs) and their nature inhibitors-the tissue inhibitors of 
metalloproteinases (TIMPs) may play a central role in these processes. The 
aggressive mechanism of pituitary adenomas was studied through investigating the 
expression of MMP-9, MMP-2, TIMP-1, and TIMP-2 in both invasive and non-invasive 
adenomas.
METHODS: Sixty-one surgical removed pituitary adenomas (forty-nine cases 
invasive and twelve non-invasive adenomas) were investigated. 
Immunohistochemistry staining (SP method) was used to detect the expression of 
MMP-9, MMP-2, TIMP-1, and TIMP-2 in two groups. The results were treated with 
semi-quantitative method and analyzed by using non-parameter rank sum test.
RESULTS: Immunohistochemical staining of tumor cells for MMP-9, TIMP-1, MMP-2, 
and TIMP-2 were noted 95.9% (47/49), 57.1% (28/49), 75.5% (37/49) and 89.8% 
(44/49) in invasive adenomas, and 100% (12/12), 91.7% (11/12), 66.7% (8/12), and 
91.7% (11/12) in non-invasive adenomas, respectively. Invasive tumors were 
significantly less expressing TIMP-1 and TIMP-2 (P < 0.05). There was no 
significant difference for MMP-9 or MMP-2 between invasive and non-invasive 
groups (P > 0.05).
CONCLUSIONS: TIMP-1 and TIMP-2 may play a key role in invasive pituitary 
adenomas to biological behavior.