Discordances in HER2 status between primary gastric cancer and corresponding metastatic sites

• Published in: Japanese journal of clinical oncology 2015-05, Vol.45 (5), p.416-421
• Main Authors: Gumusay, Ozge, Benekli, Mustafa, Ekinci, Ozgur, Baykara, Meltem, Ozet, Ahmet, Coskun, Ugur, Demirci, Umut, Uner, Aytug, Dursun, Ayse, Atak, Ecine Yesim, Buyukberber, Suleyman
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents - therapeutic use; Biomarkers, Tumor - analysis; Female; Humans; Immunohistochemistry; In Situ Hybridization - methods; Male; Middle Aged; Neoplasm Staging; Receptor, ErbB-2 - analysis; Retrospective Studies; Stomach Neoplasms - chemistry; Stomach Neoplasms - drug therapy; Stomach Neoplasms - pathology; Trastuzumab
• ISSN: 0368-2811; 1465-3621
• DOI: 10.1093/jjco/hyv020

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.