Morris C D, Gorlick R, Huvos G, Heller G, Meyers P A, Healey J H
Department of Orthopaedic Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Clin Orthop Relat Res. 2001 Jan(382):59-65. doi: 10.1097/00003086-200101000-00010.
Prognostic biologic factors that can be assessed at the time of diagnosis for patients with osteogenic sarcoma have not been identified. The current study was designed to evaluate the prognostic significance of the human epidermal growth factor receptor 2 as it relates to histologic response to preoperative chemotherapy and event-free survival. A retrospective immunohistochemical study was performed on material from patients who were newly diagnosed with osteogenic sarcoma who were treated according to the T12 protocol from the authors' institution between 1986 to 1993. Staining for HER2/erbB-2 was accomplished using standard monoclonal antibodies and methods. At the time of initial biopsy, 42.6% of the samples showed HER2/erbB-2 overexpression. Higher levels of expression were observed in samples from patients with clinically detectable metastases at initial presentation and at relapse. Expression of HER2/erbB-2 correlated with inferior event-free survival in patients with nonmetastatic disease (47% versus 79% at 5 years). In addition, HER2/erbB-2 expression was associated with significantly less tumor necrosis after preoperative chemotherapy as determined by the Huvos grading system. These data suggest that HER2/erbB-2 should be evaluated prospectively as a prognostic indicator and clinical trials using antibodies that target this receptor should be considered for the treatment of patients with osteogenic sarcoma.
目前尚未确定在骨肉瘤患者诊断时可评估的预后生物学因素。本研究旨在评估人类表皮生长因子受体2与术前化疗的组织学反应及无事件生存期的预后意义。对1986年至1993年间在作者所在机构按照T12方案治疗的新诊断骨肉瘤患者的材料进行了回顾性免疫组织化学研究。使用标准单克隆抗体和方法完成HER2/erbB-2染色。在初次活检时,42.6%的样本显示HER2/erbB-2过表达。在初次就诊和复发时临床可检测到转移的患者样本中观察到更高水平的表达。HER2/erbB-2的表达与非转移性疾病患者较差的无事件生存期相关(5年时分别为47%和79%)。此外,根据胡沃斯分级系统,HER2/erbB-2表达与术前化疗后肿瘤坏死显著减少相关。这些数据表明,应前瞻性地评估HER2/erbB-2作为预后指标,并且对于骨肉瘤患者的治疗应考虑使用靶向该受体的抗体进行临床试验。