Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
Mod Pathol. 2009 Nov;22(11):1432-8. doi: 10.1038/modpathol.2009.113. Epub 2009 Jul 24.
The biological potential of soft tissue leiomyosarcoma is difficult to predict using current standard prognostic parameters, and control of systemic disease is challenging with current chemotherapeutic protocols. Additional prognostic markers and alternative treatment options are very much required. Previous studies implicate upregulation of the oncogenic nuclear transcription factor c-Myc with aggressive behavior of many solid tumors. Therefore, this oncoprotein was evaluated as a prognostic marker for overall and metastasis-free survival in leiomyosarcoma. Immunohistochemical stains for c-Myc were performed on 28 cases of leiomyosarcoma occurring in the deep somatic soft tissues. Comparisons of Kaplan-Meier survival curves stratified by c-Myc status and conventional prognostic factors (histological grade, tumor size, and tumor stage) were evaluated using standard univariate statistical methods. A subsequent multivariate survival analysis was carried out according to the Cox proportional hazards regression model adjusting for potential confounding prognostic factors. A total of 15 cases (54%) were positive for nuclear c-Myc expression. Patients with c-Myc-positive tumors had significantly shorter metastasis-free survival intervals compared with those with c-Myc-negative tumors (median, 9 months vs. >94 months; P=0.014). c-Myc positivity also correlated with decreased overall survival (median, 23 months vs. >94 months; P=0.017). Histological grade was the only other prognostic marker predictive of poor outcome in the univariate analyses. In the multivariate survival analysis, only c-Myc status reached statistical significance, suggesting that it is an important and independent predictor of prognosis in leiomyosarcoma. Detection of nuclear c-Myc in leiomyosarcoma predicts decreased overall and metastasis-free survival, independent of standard prognostic variables, tumor size, histological grade, and TNM stage. The expression of this oncoprotein may represent a useful prognostic marker and potential therapeutic target in leiomyosarcoma.
软组织平滑肌肉瘤的生物学潜能很难用当前的标准预后参数来预测，而且目前的化疗方案也难以控制全身性疾病。非常需要额外的预后标志物和替代治疗方案。先前的研究表明，致癌核转录因子 c-Myc 的上调与许多实体瘤的侵袭性行为有关。因此，该癌蛋白被评估为平滑肌肉瘤总生存率和无转移生存率的预后标志物。对 28 例发生在深部躯体软组织中的平滑肌肉瘤进行了 c-Myc 的免疫组织化学染色。通过标准单变量统计方法比较了按 c-Myc 状态和常规预后因素（组织学分级、肿瘤大小和肿瘤分期）分层的 Kaplan-Meier 生存曲线。根据 Cox 比例风险回归模型进行了随后的多变量生存分析，该模型调整了潜在的混杂预后因素。共有 15 例（54%）为核 c-Myc 表达阳性。c-Myc 阳性肿瘤患者的无转移生存间隔明显短于 c-Myc 阴性肿瘤患者（中位数分别为 9 个月和>94 个月；P=0.014）。c-Myc 阳性也与总生存率降低相关（中位数分别为 23 个月和>94 个月；P=0.017）。组织学分级是单变量分析中唯一另一个预测不良预后的预后标志物。在多变量生存分析中，只有 c-Myc 状态具有统计学意义，表明它是平滑肌肉瘤预后的一个重要且独立的预测因素。在平滑肌肉瘤中检测到核 c-Myc 可预测总生存率和无转移生存率降低，独立于标准预后变量、肿瘤大小、组织学分级和 TNM 分期。该癌蛋白的表达可能代表一种有用的预后标志物和潜在的治疗靶点。
