Knappe Ulrich J, Hagel Christian, Lisboa Björn W, Wilczak Waldemar, Lüdecke Dieter K, Saeger Wolfgang
Department of Neurosurgery, Dr.-Horst-Schmidt-Kliniken, Ludwig-Erhard-Strasse 100, 65199, Wiesbaden, Germany.
Acta Neuropathol. 2003 Nov;106(5):471-8. doi: 10.1007/s00401-003-0747-5. Epub 2003 Aug 2.
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.
垂体腺瘤的硬脑膜侵袭性数据已与基质金属蛋白酶（如MMP-9）的表达相关联。丝氨酸蛋白酶尚未在人类垂体腺瘤中进行研究。在本研究中，对来自84例人类垂体腺瘤（肢端肥大症n = 18、库欣病n = 21、催乳素瘤n = 18、促甲状腺激素分泌腺瘤n = 1、无分泌功能腺瘤n = 26）以及9个非肿瘤性垂体前叶（取自前列腺癌患者）的石蜡包埋材料进行免疫组织化学分析，以检测MMP-2、MMP-9、金属蛋白酶组织抑制剂-2（TIMP-2）、尿激酶型纤溶酶原激活剂（uPA）、uPA受体（uPAR）、组织型纤溶酶原激活剂（tPA）、纤溶酶原激活剂抑制剂-1（PAI-1）和白细胞介素-6（IL-6）的表达。通过术前磁共振成像评估和术中检查确定海绵窦侵袭情况（侵袭性n = 50，非侵袭性n = 34）。在垂体腺瘤中，对MMP-2（74%的病例）、MMP-9（49%）、TIMP-2（88%）、uPA（89%）、uPAR（90%）、tPA（69%）和PAI-1（87%）的反应呈阳性（弥漫性表达）。在12%的腺瘤中发现IL-6表达较弱。除uPA（9例中有3例阴性）和IL-6（8例中有5例弱阳性）外，在每个垂体前叶组织样本中所有反应均呈阳性（局灶性表达）。腺瘤中uPA的表达明显高于垂体前叶组织（卡方检验P<0.05）。与非侵袭性腺瘤相比，无分泌功能腺瘤在侵袭性肿瘤中uPA过表达的趋势更强（卡方检验P = 0.053）。我们发现MMP-9表达与肿瘤侵袭无相关性。与侵袭性腺瘤相比，TIMP-2在非侵袭性腺瘤中过表达（卡方检验P<0.05）。垂体腺瘤中MMPs与丝氨酸蛋白酶之间的相互关系仍有待阐明。根据我们的数据，无法证实IL-6与MMP-9激活之间存在相关性。然而，uPA系统可能在垂体腺瘤的硬脑膜侵袭中起作用。
