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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Internal Medicine, Division of Medical Oncology, Gazi University Faculty of Medicine, Ankara ozgebostankolu@hotmail.com.
Ozge
O
Gumusay
Department of Internal Medicine, Division of Medical Oncology, Gazi University Faculty of Medicine, Ankara.
Mustafa
M
Benekli
Department of Pathology, Gazi University Faculty of Medicine, Ankara.
Ozgur
O
Ekinci
Department of Internal Medicine, Division of Medical Oncology, Sakarya Education and Research Hospital, Sakarya.
Meltem
M
Baykara
Department of Internal Medicine, Division of Medical Oncology, Gazi University Faculty of Medicine, Ankara.
Ahmet
A
Ozet
Department of Internal Medicine, Division of Medical Oncology, Gazi University Faculty of Medicine, Ankara.
Ugur
U
Coskun
Department of Internal Medicine, Division of Medical Oncology, Dr. Abdurrahman Yurtaslan Training and Research Hospital, Ankara, Turkey.
Umut
U
Demirci
Department of Internal Medicine, Division of Medical Oncology, Gazi University Faculty of Medicine, Ankara.
Aytug
A
Uner
Department of Pathology, Gazi University Faculty of Medicine, Ankara.
Ayse
A
Dursun
Department of Pathology, Gazi University Faculty of Medicine, Ankara.
Ecine Yesim
EY
Atak
Department of Internal Medicine, Division of Medical Oncology, Gazi University Faculty of Medicine, Ankara.
Suleyman
S
Buyukberber
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology*; D000068878:Trastuzumab
D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
HER2; IHC; SISH; discordance; gastric cancer