Nathanson Daniel R, Culliford Alfred T, Shia Jinru, Chen Beiyun, D'Alessio Matthew, Zeng Zhao-Shi, Nash Garrett M, Gerald William, Barany Francis, Paty Philip B
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Int J Cancer. 2003 Jul 20;105(6):796-802. doi: 10.1002/ijc.11137.
HER 2/neu is an important oncogene in breast cancer, but the prevalence and significance of HER 2/neu gene amplification in colon cancer have been poorly documented. We have evaluated HER 2/neu gene amplification and protein overexpression in a series of colon cancers to assess the frequency, concordance and clinical significance of these events. HER 2/neu gene copy number was measured in 154 primary colon tumors, 15 liver metastases and matched normal tissues using a quantitative PCR/ligase detection reaction (LDR) technique developed and validated in our laboratory. HER 2/neu copy number was confirmed by fluorescent in situ hybridization (FISH) in all tumors found to have gene amplification. In an independent and blinded fashion, HER 2/neu expression was assessed in paraffin sections from 139 of the tumor specimens using the HercepTest kit. HER 2/neu gene amplification was observed in 4 (2.4%) of the 169 tumor specimens and in none of the normal tissues. There was no apparent association with stage of disease, tumor grade or patient survival. Among 139 cases evaluated by immunohistochemistry (IHC), HER 2/neu overexpression was seen in 5 cases (3.6%). There was extremely high concordance (kappa = 0.852) between gene amplification and protein overexpression. The low prevalence of HER 2/neu gene amplification and protein overexpression suggests that this oncogene plays an infrequent role in the development and progression of colon cancer. These data indicate that the primary mechanism of dysregulated HER 2/neu expression in colon cancer, as in breast cancer, is gene amplification.
HER 2/neu是乳腺癌中的一种重要癌基因，但HER 2/neu基因扩增在结肠癌中的发生率及意义鲜有文献记载。我们评估了一系列结肠癌中HER 2/neu基因扩增及蛋白过表达情况，以评估这些事件的发生频率、一致性及临床意义。采用我们实验室开发并验证的定量PCR/连接酶检测反应（LDR）技术，对154例原发性结肠肿瘤、15例肝转移瘤及配对的正常组织进行HER 2/neu基因拷贝数测定。对所有发现有基因扩增的肿瘤，通过荧光原位杂交（FISH）确认HER 2/neu拷贝数。以独立且盲法的方式，使用HercepTest试剂盒对139例肿瘤标本的石蜡切片进行HER 2/neu表达评估。在169例肿瘤标本中，4例（2.4%）检测到HER 2/neu基因扩增，正常组织中未检测到。基因扩增与疾病分期、肿瘤分级或患者生存率无明显关联。在139例通过免疫组织化学（IHC）评估的病例中，5例（3.6%）出现HER 2/neu过表达。基因扩增与蛋白过表达之间存在极高的一致性（kappa = 0.852）。HER 2/neu基因扩增及蛋白过表达的低发生率表明，该癌基因在结肠癌的发生和发展中作用不常见。这些数据表明，与乳腺癌一样，结肠癌中HER 2/neu表达失调的主要机制是基因扩增。
