Levine E A, Holzmayer T, Bacus S, Mechetner E, Mera R, Bolliger C, Roninson I B, Das Gupta T K
Department of Surgical Oncology, University of Illinois at Chicago, USA.
J Clin Oncol. 1997 Oct;15(10):3249-57. doi: 10.1200/JCO.1997.15.10.3249.
In addition to tumor size, grade, location, and the presence of metastases, other factors may be useful in prognostication for adults with soft tissue sarcoma (STS). This study examines the relationship of MDR-1 mRNA, p-glycoprotein (P-gp), Ki-67 expression, and DNA content expression to clinical outcome in adults with STS.
Snap-frozen STS specimens from 65 patients were analyzed and compared with clinical outcomes. Immunohistochemistry was performed for the Ki-67 antigen and P-gp. DNA content was determined using the Feulgen reaction and quantitated using image analysis. MDR-1 mRNA expression was determined using a reverse-transcriptase polymerase chain reaction (RT-PCR)-based assay.
P-glycoprotein expression was found by immunohistochemistry in 48% of cases with 5-year overall (54% v 14%, P = .07) and disease-free survival rates (32% v 18%, P = .039) higher in high-grade tumors that did not express P-gp. MDR-1 mRNA was detected in 51% of cases and no patient with high levels of MDR-1 mRNA expression was a long-term survivor. Patients with diploid tumors had significantly better survival than those with nondiploid tumors (51% v 31%, P = .03). High levels of Ki-67 were associated with poorer overall survival (46% v 31%, P = .04). On multivariate analysis, American Joint Committee on Cancer (AJCC) staging, DNA content, Ki-67, and P-gp staining were significant prognostic factors for 5-year overall and disease-free survival.
P-gp expression, high-level Ki-67 expression, and nondiploid DNA content are independent prognostic indicators that correlate with poor outcomes in STS patients. However, MDR-1 mRNA was not found to be predictive of survival. These newer markers are useful additions to AJCC staging for prognostication for patients with STS. Such markers may be useful in selecting high-risk STS patients who could benefit from systemic adjuvant therapy.
除肿瘤大小、分级、位置和转移情况外，其他因素可能对软组织肉瘤（STS）成人患者的预后评估有用。本研究探讨多药耐药基因1（MDR-1）信使核糖核酸（mRNA）、P-糖蛋白（P-gp）、Ki-67表达及DNA含量表达与STS成人患者临床结局的关系。
分析65例患者的速冻STS标本，并与临床结局进行比较。对Ki-67抗原和P-gp进行免疫组织化学检测。采用福尔根反应测定DNA含量，并通过图像分析进行定量。使用基于逆转录聚合酶链反应（RT-PCR）的检测方法测定MDR-1 mRNA表达。
免疫组织化学检测发现，48%的病例中有P-gp表达，在不表达P-gp的高级别肿瘤中，5年总生存率（54%对14%，P = 0.07）和无病生存率（32%对18%，P = 0.039）更高。51%的病例检测到MDR-1 mRNA，且没有MDR-1 mRNA高表达的患者是长期存活者。二倍体肿瘤患者的生存率明显高于非二倍体肿瘤患者（51%对31%，P = 0.03）。Ki-67高水平与较差的总生存率相关（46%对31%，P = 0.04）。多因素分析显示，美国癌症联合委员会（AJCC）分期、DNA含量、Ki-67和P-gp染色是5年总生存率和无病生存率的重要预后因素。
P-gp表达、Ki-67高表达和非二倍体DNA含量是独立的预后指标，与STS患者的不良结局相关。然而，未发现MDR-1 mRNA可预测生存情况。这些新的标志物是对AJCC分期的有用补充，有助于STS患者的预后评估。此类标志物可能有助于选择可能从全身辅助治疗中获益的高危STS患者。
