Ara T, Fukuzawa M, Kusafuka T, Komoto Y, Oue T, Inoue M, Okada A
Department of Pediatric Surgery, Osaka University Medical School, Suita City, Japan.
J Pediatr Surg. 1998 Aug;33(8):1272-8. doi: 10.1016/s0022-3468(98)90167-1.
BACKGROUND/PURPOSE: The matrix metalloproteinases (MMPs) are responsible for degradation of the extracellular matrix. The MMPs and their specific tissue inhibitor metalloproteinases (TIMP) have been associated with tumor cell invasion and metastasis in a number of adult tumors. This study was carried out to detect their expression pattern in neuroblastoma and to evaluate whether they have any association with tumor progression and clinical outcome.
Cryostat sections of tumor tissues were collected from 31 patients with neuroblastoma, and immunohistochemical staining of MMP-2, MMP-9 and TIMP-2 with specific antibodies was performed according to labelled streptavidin-biotin method.
MMP-2 and MMP-9 were coexpressed in neuroblastoma and exhibited an intratumor variability of staining intensity. MMP-2 and MMP-9 staining were confined mostly to the peritumoral stromal tissues rather than tumor cells and found positive in 80.6% cases and 71.0% cases, respectively. MMP-2 and MMP-9 immunoreactivity had no association with mass screened cases or with age of the patients. Increased expression of MMP-2 in stromal tissues of neuroblastoma had significant association with advanced clinical stages (chi2 test, P < .05). However, the expression of MMP-9 in neuroblastoma had no association with clinical stages and prognosis. However, TIMP-2 staining was confined mostly to the neoplastic cell cytoplasm, stromal tissue, and to the endothelial cells and accounted for 58.0% positivity. Decreased expression of TIMP-2 also had significant relationship with advanced clinical stages (chi2 test, P < .05). Kaplan-Meier survival curve showed that either increased expression of MMP-2 or decreased expression of TIMP-2 had relationship with poor clinical outcome.
In neuroblastoma, stromal tissues are actively involved in the complex interaction between MMP-2 and TIMP-2 in extracellular matrix degradation during tumor progression, and TIMP-2 expression is inversely correlated with the corresponding MMP-2. An early detection of their expression pattern by immunohistochemistry in neuroblastoma may provide prognostic informations in clinical practice.
背景/目的：基质金属蛋白酶（MMPs）负责细胞外基质的降解。MMPs及其特异性组织抑制金属蛋白酶（TIMP）在多种成人肿瘤中与肿瘤细胞侵袭和转移相关。本研究旨在检测它们在神经母细胞瘤中的表达模式，并评估它们是否与肿瘤进展及临床结局有关。
收集31例神经母细胞瘤患者肿瘤组织的冰冻切片，采用标记链霉亲和素-生物素法用特异性抗体对MMP-2、MMP-9和TIMP-2进行免疫组织化学染色。
MMP-2和MMP-9在神经母细胞瘤中共同表达，且染色强度在肿瘤内存在差异。MMP-2和MMP-9染色主要局限于肿瘤周围的基质组织而非肿瘤细胞，分别在80.6%和71.0%的病例中呈阳性。MMP-2和MMP-9免疫反应性与筛查病例或患者年龄无关。神经母细胞瘤基质组织中MMP-2表达增加与临床晚期显著相关（卡方检验，P<.05）。然而，神经母细胞瘤中MMP-9的表达与临床分期和预后无关。然而，TIMP-2染色主要局限于肿瘤细胞质、基质组织和内皮细胞，阳性率为58.0%。TIMP-2表达降低也与临床晚期显著相关（卡方检验，P<.05）。Kaplan-Meier生存曲线显示，MMP-2表达增加或TIMP-2表达降低均与不良临床结局有关。
在神经母细胞瘤中，基质组织在肿瘤进展过程中积极参与MMP-2和TIMP-2在细胞外基质降解中的复杂相互作用，且TIMP-2表达与相应的MMP-2呈负相关。通过免疫组织化学早期检测神经母细胞瘤中它们的表达模式可能为临床实践提供预后信息。
