He Dong-sheng, Chen Ming-zhen, Wang Hai-jun, Ke Chun-long, Yan Chao, Zheng Heng, Hong Yi-shan
Department of Neurosurgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.
Ai Zheng. 2002 Oct;21(10):1124-8.
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.
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.
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).
TIMP-1 and TIMP-2 may play a key role in invasive pituitary adenomas to biological behavior.
垂体腺瘤通常组织学上为良性且生长缓慢，但其中一部分会具有局部侵袭性，发展为侵袭性垂体腺瘤。肿瘤行为存在这些差异的原因尚不清楚。垂体腺瘤血管丰富。血管生成和肿瘤侵袭都需要细胞外基质成分降解以允许细胞迁移。基质金属蛋白酶（MMPs）及其天然抑制剂——金属蛋白酶组织抑制剂（TIMPs）可能在这些过程中起核心作用。通过研究MMP - 9、MMP - 2、TIMP - 1和TIMP - 2在侵袭性和非侵袭性腺瘤中的表达，探讨垂体腺瘤的侵袭机制。
对61例手术切除的垂体腺瘤（49例侵袭性腺瘤和12例非侵袭性腺瘤）进行研究。采用免疫组织化学染色（SP法）检测两组中MMP - 9、MMP - 2、TIMP - 1和TIMP - 2的表达。结果采用半定量方法处理，并使用非参数秩和检验进行分析。
侵袭性腺瘤中肿瘤细胞MMP - 9、TIMP - 1、MMP - 2和TIMP - 2的免疫组织化学染色阳性率分别为95.9%（47/49）、57.1%（28/49）、75.5%（37/49）和89.8%（44/49），非侵袭性腺瘤中分别为100%（12/12）、91.7%（11/12）、66.7%（8/12）和91.7%（11/12）。侵袭性肿瘤中TIMP - 1和TIMP - 2的表达明显较低（P < 0.05）。侵袭性和非侵袭性组之间MMP - 9或MMP - 2无显著差异（P > 0.05）。
TIMP - 1和TIMP - 2可能在侵袭性垂体腺瘤的生物学行为中起关键作用。
