Benassi Maria Serena, Pazzaglia Laura, Chiechi Antonella, Alberghini Marco, Conti Amalia, Cattaruzza Sabrina, Wassermann Bruna, Picci Piero, Perris Roberto
Laboratory of Oncology Research, Rizzoli Orthopaedic Institute, Bologna, Italy.
J Orthop Res. 2009 Jan;27(1):135-40. doi: 10.1002/jor.20694.
Enhanced expression levels of NG2 proteoglycan in presurgical original lesions of soft-tissue sarcoma (STS) patients defines with 55% probability the immediate (i.e., within 12 months postsurgery) risk in these individuals to develop postsurgical secondary lesions, independently of any other clinical trait. It, therefore, provides a molecular factor that alone prospects a particularly unfavorable clinical outcome in such patients. Evaluation of the timing of metastasis formation in patients with high and low levels of NG2 in their primitive lesions further stratified the patients in subsets with diverse lag phases in the occurrence of metastatic disease. In our cohort of high-grade STS cases, transcription of NG2 also showed a 81-fold amplification in metastatic lesions, when compared to primitive ones, and this gene overexpression was accompanied by an abundant but nonuniform in situ expression of its product. In a similar manner as seen in primitive lesions, patients with higher levels of metastatic NG2 encountered a significantly more dismal clinical course. Multivariate analysis asserted that in these individuals upregulation of NG2 represented an absolute independent prognostic parameter. Therefore, minimally invasive assessment of the transcription levels of the NG2 gene represents a parameter capable of predicting the arising of metastatic disease within a definite postsurgery time interval, and affords in adjunct in the definition of life expectance in STS patients.
软组织肉瘤(STS)患者术前原发灶中NG2蛋白聚糖表达水平升高,有55%的概率可确定这些个体术后(即术后12个月内)发生继发性病变的直接风险,且独立于任何其他临床特征。因此,它提供了一个分子因素,仅这一因素就预示着此类患者的临床结局特别不利。对原发灶中NG2水平高低不同的患者转移形成时间的评估,进一步将患者分层为转移疾病发生时有不同滞后阶段的亚组。在我们的高级别STS病例队列中,与原发灶相比,转移灶中NG2的转录也显示出81倍的扩增,并且该基因的过表达伴随着其产物丰富但不均匀的原位表达。与原发灶情况类似,转移灶中NG2水平较高的患者临床病程明显更差。多变量分析表明,在这些个体中,NG2的上调是一个绝对独立的预后参数。因此,对NG2基因转录水平进行微创评估是一个能够预测在特定术后时间间隔内转移疾病发生的参数,并有助于确定STS患者的预期寿命。