Schoedel K E, Greco M A, Stetler-Stevenson W G, Ohori N P, Goswami S, Present D, Steiner G C
Department of Pathology, Hospital for Joint Diseases, New York, NY, USA.
Hum Pathol. 1996 Nov;27(11):1144-8. doi: 10.1016/s0046-8177(96)90306-8.
The clinical behavior of giant cell tumors (GCTs) is unpredictable. To gain insight into this tumor's biological behavior, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) were studied. These substances play essential roles in wound healing and neoplastic invasion and metastasis. Paraffin-embedded tissue was collected from 18 cases of histologically benign GCT, with 17 treated by curettage and 1 by resection. Eight cases showed no recurrence after a minimum of 2.5 years, and 10 had local recurrence. One showed metastasis. Antibodies to MMP-9, MMP-2, TIMP-1, and TIMP-2 were applied by immunohistochemical methods. In all cases, MMP-9 was strongly expressed in giant cells predominantly in a diffuse pattern and was strong but focal in stromal cells. MMP-2 decorated stromal cells and giant cells heterogeneously. TIMP-1 was variably expressed in giant cells of the nonrecurrent cases and was strongly present in a diffuse or patchy distribution in the stromal cells in 6 of 8 cases. However, in 9 of 10 recurrent cases, TIMP-1 was expressed weakly by both giant and stromal cells. TIMP-2 was variably expressed in the giant cells of the nonrecurrent cases, but 6 of 8 nonrecurrent cases showed strong stromal cell positivity for TIMP-2. Weak staining for TIMP-2 was observed in 7 of 10 recurrent cases in the stromal cells and 9 of 10 recurrent cases in the giant cells. These results indicate that expression of MMPs and TIMPs differs in giant cells and stromal cells in the same tumor. More significantly, in contrast to the nonrecurrent giant cell tumors, there is an imbalance in the MMPs and TIMPs in the recurrent tumors with a net excess of MMPs. This unopposed expression of MMPs in GCTs may play a role in breakdown of extracellular matrix and tissue invasion. Finally, these markers may prove useful in predicting behavior in these tumors.
骨巨细胞瘤（GCTs）的临床行为难以预测。为深入了解该肿瘤的生物学行为，对基质金属蛋白酶（MMPs）和金属蛋白酶组织抑制剂（TIMPs）进行了研究。这些物质在伤口愈合以及肿瘤侵袭和转移过程中发挥着重要作用。从18例组织学上为良性的骨巨细胞瘤中收集石蜡包埋组织，其中17例采用刮除术治疗，1例采用切除术治疗。8例在至少2.5年后未复发，10例出现局部复发。1例发生转移。采用免疫组织化学方法应用针对MMP - 9、MMP - 2、TIMP - 1和TIMP - 2的抗体。在所有病例中，MMP - 9在巨细胞中主要以弥漫性模式强烈表达，在基质细胞中表达强烈但呈局灶性。MMP - 2在基质细胞和巨细胞中呈异质性分布。TIMP - 1在未复发病例的巨细胞中表达各异，在8例中的6例基质细胞中以弥漫性或斑片状分布强烈表达。然而，在10例复发病例中的9例中，巨细胞和基质细胞中TIMP - 1均弱表达。TIMP - 2在未复发病例的巨细胞中表达各异，但8例未复发病例中的6例基质细胞对TIMP - 2呈强阳性。在10例复发病例中的7例基质细胞和10例复发病例中的9例巨细胞中观察到TIMP - 2染色较弱。这些结果表明，在同一肿瘤的巨细胞和基质细胞中，MMPs和TIMPs的表达存在差异。更显著的是，与未复发的骨巨细胞瘤相比，复发肿瘤中MMPs和TIMPs失衡，MMPs净过量。骨巨细胞瘤中MMPs的这种无对抗表达可能在细胞外基质的破坏和组织侵袭中起作用。最后，这些标志物可能在预测这些肿瘤的行为方面证明是有用的。
