干扰素-α/β 受体作为骨肉瘤的预后标志物。

Interferon-α/β receptor as a prognostic marker in osteosarcoma.

机构信息

Department of Orthopaedic Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Japan.

出版信息

J Bone Joint Surg Am. 2011 Mar 16;93(6):519-26. doi: 10.2106/JBJS.J.00198.

DOI:10.2106/JBJS.J.00198

PMID:21411701

Abstract

BACKGROUND

A large-scale randomized trial of adjuvant interferon-α therapy for patients with osteosarcoma has been initiated as a joint protocol by the European and American Osteosarcoma Study Group. Because the expression of functional interferon-α/β receptor is necessary for interferon-α agents to interact with osteosarcoma cells, we examined the expression of interferon-α/β receptor in a series of osteosarcoma specimens.

METHODS

Forty patients with high-grade resectable osteosarcoma, from whom surgical specimens had been obtained at the time of biopsy, were included in this retrospective study. Biopsy specimens were immunohistochemically stained with anti-interferon-α/β receptor antibodies. Survival was estimated with the Kaplan-Meier method. The Cox proportional hazards model was used for multivariate analysis to determine the independent prognostic factors. Furthermore, we used Holm and Benjamini-Hochberg procedures to adjust for multiple comparisons in setting the level of significance. The median follow-up period was five years and two months (range, four to 195 months).

RESULTS

The expression of interferon-α/β receptor was positive in eighteen (45%) of the forty patients with high-grade osteosarcoma. American Joint Committee on Cancer surgical stage IIA, a good histologic response to chemotherapy, and expression of interferon-α/β receptor correlated significantly with better disease-free survival (p < 0.05). Multivariate analysis showed that interferon-α/β receptor expression alone retained its power to predict an improved prognosis (p = 0.042). There were no significant variables after corrections for multiple comparisons.

CONCLUSIONS

Interferon-α/β receptor may be a useful marker for assessing tumor prognosis in patients with osteosarcoma and may play an important role in tumor progression. These findings are encouraging and support the ongoing clinical trials of adjuvant interferon-α therapy by the multinational Osteosarcoma Study Group. Our pilot study was based on a small sample size, and larger trials are needed to confirm this finding.

LEVEL OF EVIDENCE

Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.

摘要

背景

一项针对骨肉瘤患者辅助干扰素-α 治疗的大规模随机试验已作为欧美骨肉瘤研究组的联合方案启动。因为功能性干扰素-α/β 受体的表达对于干扰素-α 药物与骨肉瘤细胞相互作用是必要的，所以我们检测了一系列骨肉瘤标本中干扰素-α/β 受体的表达。

方法

本回顾性研究纳入了 40 例高级可切除骨肉瘤患者，他们在活检时获得了手术标本。活检标本用抗干扰素-α/β 受体抗体进行免疫组织化学染色。采用 Kaplan-Meier 法估计生存率。Cox 比例风险模型用于多变量分析，以确定独立的预后因素。此外，我们使用 Holm 和 Benjamini-Hochberg 程序在设定显著性水平时进行多重比较的调整。中位随访时间为 5 年 2 个月（范围 4 至 195 个月）。

结果

在 40 例高级骨肉瘤患者中，有 18 例（45%）表达干扰素-α/β 受体。美国癌症联合委员会（AJCC）分期 IIA、化疗后组织学反应良好和干扰素-α/β 受体的表达与无病生存率的提高显著相关（p<0.05）。多变量分析显示，干扰素-α/β 受体的表达单独保留了预测预后改善的能力（p=0.042）。在进行多次比较校正后，没有显著的变量。