Serum HER2 levels and HER2 status in tumor cells in advanced gastric cancer patients.
OBJECTIVE
Increased serum human epidermal growth factor receptor 2 levels have been found in metastatic breast cancer patients and are correlated with human epidermal growth factor receptor 2 overexpression in tumor cells. However, the prevalence of serum human epidermal growth factor receptor 2 in gastric cancer patients has not been elucidated.


METHODS
We retrospectively analyzed formalin-fixed paraffin-embedded tumor tissues and serum samples from 96 advanced gastric cancer patients. Human epidermal growth factor receptor 2 expression and gene amplification in tumor cells were determined by immunohistochemistry and fluorescence in situ hybridization. Serum human epidermal growth factor receptor 2 levels were measured using a chemiluminescent immunoassay. Human epidermal growth factor receptor 2 positivity in tumor cells was defined as immunohistochemistry 2+ with fluorescence in situ hybridization positive or immunohistochemistry 3+ with any fluorescence in situ hybridization results.


RESULTS
All tissue samples and serum samples were successfully measured. Nineteen patients (20%) were human epidermal growth factor receptor 2-positive in tumor cells. The median serum human epidermal growth factor receptor 2 level was 9.3 ng/ml (range, 5.0-332.4 ng/ml), and serum human epidermal growth factor receptor 2 levels were significantly separated according to human epidermal growth factor receptor 2 status in tumor cells (P < 0.0001, Wilcoxon's rank sum test); median serum human epidermal growth factor receptor 2 levels in human epidermal growth factor receptor 2-negative patients and -positive patients were 8.9 (range, 5.0-20.5) and 24.0 (range, 9.7-332.4), respectively. There were 15 serum human epidermal growth factor receptor 2-positive patients (16%) using a cutoff value of 15 ng/ml. The sensitivity and the specificity of serum human epidermal growth factor receptor 2 with respect to human epidermal growth factor receptor 2 positivity in tumor cells were 53 and 94%, respectively.


CONCLUSIONS
Serum human epidermal growth factor receptor 2 measurements cannot be substituted for tissue human epidermal growth factor receptor 2 diagnosis in advanced gastric cancer patients. However, serum human epidermal growth factor receptor 2 levels are associated with human epidermal growth factor receptor 2 overexpression in tumor cells. Further investigations of clinical significance of serum human epidermal growth factor receptor 2 as a predictive marker and a therapy-monitoring marker are warranted.
Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo.
Takahide
T
Sasaki
Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa nofuse@east.ncc.go.jp.
Nozomu
N
Fuse
Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa.
Takeshi
T
Kuwata
Biostatistics Division, Center for Research Administration and Support, National Cancer Center, Kashiwa.
Shogo
S
Nomura
Department of Gastroenterology, Endoscopy Division, National Cancer Center Hospital East, Kashiwa.
Kazuhiro
K
Kaneko
Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa.
Toshihiko
T
Doi
Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa.
Takayuki
T
Yoshino
Siemens Healthcare Diagnostics, Tokyo.
Hiromichi
H
Asano
Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa.
Atsushi
A
Ochiai
Cancer Center, Hokkaido University Hospital, Sapporo, Japan.
Yoshito
Y
Komatsu
Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo.
Naoya
N
Sakamoto
Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa.
Atsushi
A
Ohtsu
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood*; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000097:blood*; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000097:blood / Q000737:chemistry* / Q000473:pathology*; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
HER2; diagnostic marker; gastric cancer; tumor marker