Gumusay Ozge, Benekli Mustafa, Ekinci Ozgur, Baykara Meltem, Ozet Ahmet, Coskun Ugur, Demirci Umut, Uner Aytug, Dursun Ayse, Atak Ecine Yesim, Buyukberber Suleyman
Department of Internal Medicine, Division of Medical Oncology, Gazi University Faculty of Medicine, Ankara
Department of Internal Medicine, Division of Medical Oncology, Gazi University Faculty of Medicine, Ankara.
Jpn J Clin Oncol. 2015 May;45(5):416-21. doi: 10.1093/jjco/hyv020. Epub 2015 Mar 2.
Determination of human epidermal growth factor receptor-2 status in advanced gastric cancer is important in clinical decision making. In the trastuzumab for GC trial, trastuzumab-based therapy demonstrated a significant overall survival benefit in patients with human epidermal growth factor receptor-2-positive advanced gastric cancer. Human epidermal growth factor receptor-2 discordance in gastric cancer primary and its metastases has been long debated. The aim of the study was to evaluate the rate of human epidermal growth factor receptor-2 discordance and its effect on treatment decisions in advanced gastric cancer.
A total of 74 patients with advanced gastric cancer were included in the study. Both immunohistochemical staining and dual-color silver in situ hybridization were performed in all patients to evaluate the human epidermal growth factor receptor-2 status of the primary lesion and paired metastasis.
The assessment of human epidermal growth factor receptor-2 status with the immunohistochemical staining method and dual-color silver in situ hybridization revealed a discordance rate of 9.5 and 16.2%, respectively. However, this discordance was clinically meaningful in only one patient leading to a change in treatment decision. While this patient had a human epidermal growth factor receptor-2-negative status in primary tumor (immunohistochemical = 0, dual-color silver in situ hybridization = negative), the human epidermal growth factor receptor-2 status was positive for liver metastasis (immunohistochemical = 2+, dual-color silver in situ hybridization = positive). Trastuzumab was added to the chemotherapy regimen.
In this study, we found a higher rate of human epidermal growth factor receptor-2 discordance between primary gastric tumor and metastatic lesions compared with the rates reported in previous studies. Detection of a human epidermal growth factor receptor-2-positive metastasis with a human epidermal growth factor receptor-2-negative primary tumor suggests that investigation of human epidermal growth factor receptor-2 is also required for the metastatic lesion and that trastuzumab could be administered in the case of a positive result.
确定人表皮生长因子受体2（HER-2）状态对于晚期胃癌的临床决策至关重要。在胃癌曲妥珠单抗试验中，基于曲妥珠单抗的治疗方案在HER-2阳性晚期胃癌患者中显示出显著的总生存获益。胃癌原发灶与其转移灶之间HER-2不一致性一直存在争议。本研究旨在评估晚期胃癌中HER-2不一致率及其对治疗决策的影响。
本研究共纳入74例晚期胃癌患者。对所有患者均进行免疫组织化学染色和双色银原位杂交，以评估原发灶及配对转移灶的HER-2状态。
免疫组织化学染色法和双色银原位杂交法评估HER-2状态的不一致率分别为9.5%和16.2%。然而，这种不一致仅在1例患者中具有临床意义，导致了治疗决策的改变。该患者原发肿瘤HER-2阴性（免疫组织化学=0，双色银原位杂交=阴性），而肝转移灶HER-2阳性（免疫组织化学=2+，双色银原位杂交=阳性）。于是在化疗方案中加入了曲妥珠单抗。
在本研究中，我们发现与既往研究报道的比率相比，原发性胃癌肿瘤与转移病灶之间HER-2不一致率更高。原发性肿瘤HER-2阴性而转移灶HER-2阳性表明，对于转移病灶也需要检测HER-2，若结果为阳性则可给予曲妥珠单抗治疗。
