TY - JOUR
T1 - Serum HER2 as an adjunct to assess HER2 status for advanced gastric cancer
T2 - A prospective multicenter trial (SHERLOCK)
AU - Saito, Mayuko
AU - Yamashita, Kentaro
AU - Arimura, Yoshiaki
AU - Kaneto, Hiroyuki
AU - Okuda, Hiroyuki
AU - Nojima, Masanori
AU - Hagiwara, Takeshi
AU - Suzuki, Kazuya
AU - Adachi, Takeya
AU - Goto, Akira
AU - Nakachi, Kohei
AU - Yawata, Atsushi
AU - Yoshimoto, Mitsuru
AU - Tanuma, Tokuma
AU - Adachi, Yasushi
AU - Yamaoka, Satoshi
AU - Mizukoshi, Tsunenori
AU - Kawayama, Mariko
AU - Hamamoto, Yasuo
AU - Shinomura, Yasuhisa
N1 - Funding Information:
Declaration of interest MS has received honoraria from Chugai and Takeda. KY has received research funding from Taiho and received honoraria from Chugai, Takeda and Ajinomoto. YA has received research funding from Astellas, AstraZeneca, Eizai and Takeda and received honoraria from Kyorin and Takeda. YH has received honoraria from Chugai. YS has received research funding from Pfizer, Novartis, Chugai and Daiichi Sankyo, and received honoraria from Eizai, Daiichi Sankyo, and Mitsubishi-Tanabe. All remaining authors have declared no conflicts of interest. The funding source of the study had no role in study design; in the collection, analysis, and interpretation of the data; or in the writing of this report.
Publisher Copyright:
© 2016 Taylor & Francis.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Background: Intratumoral human epidermal growth factor receptor 2 (HER2) heterogeneity of gastric cancer can be an obstacle to accurate HER2 assessment. Serum HER2, concentrations of the HER2 extracellular domain shed into the bloodstream, has a potential to compensate HER2 immunohistochemistry (IHC) but has not been scrutinized in gastric cancer. This study sought to explore the clinical utility of serum HER2 in gastric cancer. Methods: We performed a prospective multicenter trial (SHERLOCK trial) involving patients with allstage gastric or gastro-esophageal junction cancer. Serum HER2 was measured using direct chemiluminescence while tissue HER2 status was determined using IHC and fluorescent in situ hybridization. For stage IV cases, concordance between local and central laboratories in tissue HER2 assessment was also evaluated. Results: Of 224 patients enrolled, both tissue HER2 status and serum HER2 levels were successfully determined in 212 patients and 21% (45/212) were tissue HER2-positive. Serum HER2 levels, ranged from 4.5 to 148.0 ng/ml (median 10.3), correlated with tissue HER2 status (p=0.003). At a cut-off level of 28.0 ng/ml determined by receiver operating characteristics analysis, sensitivity, specificity, positive and negative predictive values of serum HER2 were 22.6%, 100%, 100% and 82.3%, respectively. All nine cases with elevated serum HER2 were tissue HER2-positive stage IV cases. Among 61 stage IV cases, the agreement rate for IHC scoring between the local and the central laboratories was 82% and tissue HER2 judgment was conflicting in five (8.2%) cases. Of these five cases, four were confirmed as false-negative and two of these four patients demonstrated elevated serum HER2. Conclusions: Serum HER2 levels correlated with tissue HER2 status in gastric cancer. Although the low sensitivity is a drawback, serum HER2 might be a useful adjunct tool to detect tissue HER2 false-negative gastric cancer.
AB - Background: Intratumoral human epidermal growth factor receptor 2 (HER2) heterogeneity of gastric cancer can be an obstacle to accurate HER2 assessment. Serum HER2, concentrations of the HER2 extracellular domain shed into the bloodstream, has a potential to compensate HER2 immunohistochemistry (IHC) but has not been scrutinized in gastric cancer. This study sought to explore the clinical utility of serum HER2 in gastric cancer. Methods: We performed a prospective multicenter trial (SHERLOCK trial) involving patients with allstage gastric or gastro-esophageal junction cancer. Serum HER2 was measured using direct chemiluminescence while tissue HER2 status was determined using IHC and fluorescent in situ hybridization. For stage IV cases, concordance between local and central laboratories in tissue HER2 assessment was also evaluated. Results: Of 224 patients enrolled, both tissue HER2 status and serum HER2 levels were successfully determined in 212 patients and 21% (45/212) were tissue HER2-positive. Serum HER2 levels, ranged from 4.5 to 148.0 ng/ml (median 10.3), correlated with tissue HER2 status (p=0.003). At a cut-off level of 28.0 ng/ml determined by receiver operating characteristics analysis, sensitivity, specificity, positive and negative predictive values of serum HER2 were 22.6%, 100%, 100% and 82.3%, respectively. All nine cases with elevated serum HER2 were tissue HER2-positive stage IV cases. Among 61 stage IV cases, the agreement rate for IHC scoring between the local and the central laboratories was 82% and tissue HER2 judgment was conflicting in five (8.2%) cases. Of these five cases, four were confirmed as false-negative and two of these four patients demonstrated elevated serum HER2. Conclusions: Serum HER2 levels correlated with tissue HER2 status in gastric cancer. Although the low sensitivity is a drawback, serum HER2 might be a useful adjunct tool to detect tissue HER2 false-negative gastric cancer.
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U2 - 10.3109/0284186X.2015.1107189
DO - 10.3109/0284186X.2015.1107189
M3 - Article
C2 - 26757197
AN - SCOPUS:84954229382
SN - 0284-186X
VL - 55
SP - 309
EP - 317
JO - Acta Oncologica
JF - Acta Oncologica
IS - 3
ER -
