title: Expression of serine proteases and metalloproteinases in human pituitary adenomas and anterior pituitary lobe tissue.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Dr.-Horst-Schmidt-Kliniken, Ludwig-Erhard-Strasse 100, 65199, Wiesbaden, Germany. Ulrich.Knappe@hsk-wiesbaden.de
authors.forename: Ulrich J
authors.initials: UJ
authors.lastname: Knappe
authors.forename: Christian
authors.initials: C
authors.lastname: Hagel
authors.forename: Björn W
authors.initials: BW
authors.lastname: Lisboa
authors.forename: Waldemar
authors.initials: W
authors.lastname: Wilczak
authors.forename: Dieter K
authors.initials: DK
authors.lastname: Lüdecke
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Saeger
mesh_terms: D000236:Adenoma / Q000201:enzymology*; D000293:Adolescent; D000328:Adult; D000974:Antibodies, Antinuclear / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002452:Cell Count; D005260:Female; D006065:Gonadotropins, Pituitary / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D010903:Pituitary Gland, Anterior / Q000201:enzymology*; D010911:Pituitary Neoplasms / Q000201:enzymology*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D006065:Gonadotropins, Pituitary; D015850:Interleukin-6; D019394:Ki-67 Antigen; C440408:MIB-1 antibody; D017395:Plasminogen Activator Inhibitor 1; D019716:Tissue Inhibitor of Metalloproteinase-2; D012697:Serine Endopeptidases; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9