In this study, the predictive roles of matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 and 2 in invasive and noninvasive prolactinomas were examined. Prognostic biomarkers to distinguish between invasive and noninvasive pituitary adenomas are required for the effective treatment of pituitary adenoma patients. We analyzed 57 prolactinoma patients classified as having invasive and noninvasive adenomas for MMP-9, TIMP-1 and TIMP-2 expression using immunohistochemical methods. Significantly higher MMP-9 expression was detected in invasive prolactinomas (p = 0.004). There was also a significant relationship between TIMP-2 expression and invasive behavior (p = 0.004) and TIMP-2 expression and recurrence (p = 0.005). Because MMP-9 expression is significantly increased in invasive prolactinomas, MMP-9 has potential as a marker for invasion. TIMP-2 may be a marker for both invasion and recurrence. These findings require further examination in large scale prospective studies. (C) 2015 Elsevier Ltd. All rights reserved.