Onda M, Matsuda S, Higaki S, Iijima T, Fukushima J, Yokokura A, Kojima T, Horiuchi H, Kurokawa T, Yamamoto T
Department of Oncology, University of Tokyo, Shirokanedai, Japan.
Cancer. 1996 Jan 1;77(1):71-8. doi: 10.1002/(SICI)1097-0142(19960101)77:1<71::AID-CNCR13>3.0.CO;2-5.
It has been reported that the c-erbB-2 protooncogene is frequently amplified and overexpressed in many types of cancers, except sarcomas and hematological malignancies.
Expression of ErbB-2 in the tumors of 26 patients with conventional osteosarcoma was evaluated by immunoblotting. DNA from osteosarcoma tissues that expressed ErbB-2 were analyzed by Southern blot hybridization to examine gross rearrangement of the gene. The DNA was also surveyed for the presence of genetic mutation in the transmembrane domain of ErbB-2 by polymerase chain reaction-single-stranded DNA conformation polymorphism analysis. In addition, possible correlation of ErbB-2 expression with gender, age, histopathologic subtype, and response to chemotherapy was analyzed. Survival analysis was performed by the Kaplan-Meier test using the approximate chi-square statistic for the log-rank test.
The ErbB-2 protein was detected in 11 of 26 osteosarcoma tissues (42%) by immunoblot analysis. Expression of ErbB-2 was confirmed by immunohistochemical studies using specific anti-ErbB-2 monoclonal antibody. However, neither amplification of the c-erbB-2 gene nor evidence of significant genetic mutation was found in these osteosarcomas. Expression of ErbB-2 examined by immunoblotting was most strongly correlated with early pulmonary metastases (P < 0.05). Among the entire group of 26 patients in this study, Kaplan-Meier life table survival of the patients with apparent ErbB-2 expression was significantly worse than that of the patients with little ErbB-2 expression (P < 0.01).
In 42% of the osteosarcomas, the tumor cells expressed ErbB-2. Expression of ErbB-2 was strongly correlated with early pulmonary metastasis and poor survival rate for the patient. These data suggest that ErbB-2 plays a significant role in aggressive tumor growth and in the promotion of metastatic potential in osteosarcomas. ErbB-2 in the osteosarcoma tissues would be a useful prognostic marker for patients.
据报道，除肉瘤和血液系统恶性肿瘤外，c-erbB-2原癌基因在多种癌症中经常发生扩增和过表达。
通过免疫印迹法评估26例传统骨肉瘤患者肿瘤中ErbB-2的表达。对表达ErbB-2的骨肉瘤组织的DNA进行Southern印迹杂交分析，以检测该基因的总体重排。还通过聚合酶链反应-单链DNA构象多态性分析检测DNA中ErbB-2跨膜结构域的基因突变情况。此外，分析了ErbB-2表达与性别、年龄、组织病理学亚型及化疗反应之间可能的相关性。采用Kaplan-Meier检验进行生存分析，并使用对数秩检验的近似卡方统计量。
通过免疫印迹分析，在26例骨肉瘤组织中的11例（42%）检测到了ErbB-2蛋白。使用特异性抗ErbB-2单克隆抗体的免疫组织化学研究证实了ErbB-2的表达。然而，在这些骨肉瘤中未发现c-erbB-2基因扩增或明显基因突变的证据。通过免疫印迹检测的ErbB-2表达与早期肺转移最密切相关（P < 0.05）。在本研究的26例患者中，明显表达ErbB-2的患者的Kaplan-Meier生存寿命表显著低于ErbB-2表达较少的患者（P < 0.01）。
在42%的骨肉瘤中，肿瘤细胞表达ErbB-2。ErbB-2表达与早期肺转移及患者的低生存率密切相关。这些数据表明，ErbB-2在骨肉瘤侵袭性肿瘤生长和转移潜能促进中起重要作用。骨肉瘤组织中的ErbB-2可能是患者有用的预后标志物。
