MMP-13 and p53 in the progression of malignant peripheral nerve sheath tumors
MMP-13 and p53 in the progression of malignant peripheral nerve sheath tumors
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DOI：
10.1593/neo.07304
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发表时间：
2007-08-01
期刊：
影响因子：
4.8
通讯作者：
von Deimling, Andreas
中科院分区：
文献类型：
--
作者：
Holtkamp, Nikola;Atallah, Isis;von Deimling, Andreas
恶性周围神经鞘瘤(MPNST)是一种预后较差、治疗选择有限的肉瘤。导致肿瘤进展的因素在很大程度上是未知的。因此，我们检测了22例1型神经纤维瘤病(NF1)患者、14例非NF1患者和14例神经纤维瘤患者的MPNST中基质金属蛋白酶13(MMP13)的表达。由于野生型和突变型P53对基质金属蛋白酶-13的表达有不同的调节作用，因此我们还确定了TP53的状态和蛋白水平。MPNST中有58%的组织中有MMP13的表达，且与MPNST的复发显著相关(P=0.019)。P53蛋白在78%的MPNST中阳性表达，且与MMP13的表达密切相关(P=0.005)。相反，14例神经纤维瘤缺乏基质金属蛋白酶-13和p53的表达。仅有11%的MPNST中发现TP53突变，且与高肿瘤分级相关(P=0.029)。未观察到突变型TP53与基质金属蛋白酶-13之间的显著关联，表明其他因素推动了MPNST中基质金属蛋白酶-13的表达。转移的存在与p53Pro(72)基因多态性和较短的生存期有关(P=.041)。综上所述，我们的数据表明，神经鞘肿瘤中的基质金属蛋白酶-13的表达与恶性进展有关。因此，基质金属蛋白酶-13可作为肿瘤进展的标志物和治疗靶点。
Malignant peripheral nerve sheath tumors ( MPNST) are sarcomas with poor prognosis and limited treatment options. Factors contributing to tumor progression are largely unknown. We therefore examined MPNST from 22 neurofibromatosis type 1 (NF1) patients, 14 non-NF1 patients, and 14 neurofibroma patients for matrix metalloproteinase 13 (MMP-13) expression. Because wild-type and mutant p53 were shown to differentially regulate MMP-13 expression, TP53 status and protein levels were also determined. MMP-13 expression was detected in 58% of MPNST and was significantly associated with recurrent MPNST (P =.019). p53 was observed in 78% of MPNST and was found to be strongly associated with MMP- 13 expression ( P =.005). In contrast, 14 neurofibromas lacked MMP- 13 and p53 expressions. TP53 mutations were found in only 11% of MPNST and were associated with high tumor grades (P=.029). No significant association between mutant TP53 and MMP- 13 was observed, indicating that other factors drive MMP- 13 expression in MPNST. The presence of metastasis was linked to p53Pro(72) polymorphism (P=.041) and shorter survival. In summary, our data suggest that MMP-13 expression in nerve sheath tumors is coupled with malignant progression. Therefore, MMP- 13 may serve as a marker for progression and as a therapeutic target.