Serum HER2 Extracellular Domain as a Potential Alternative for Tissue HER2 Status in Metastatic Gastric Cancer Patients

Peng, Zhi; Liu, Yi; Li, Yanyan; Zhang, Xiaotian; Zhou, Jun; Lu, Ming; Li, Qingqing; Shen, Lin

doi:10.2217/bmm.14.10

Cited by 15 publications

(13 citation statements)

References 22 publications

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“…Changes in circulating HER2 levels during chemotherapy were reported to be associated with clinical outcomes in HER2-positive gastric cancer patients receiving trastuzumab and chemotherapy [21,22]. Although we observed a decrease in serum HER2 levels in our study, such decreases simply appeared to reflect tumor shrinkage.…”

Section: Discussioncontrasting

confidence: 74%

“…Circulating HER2 was expected to be a predictive marker for HER2 expression in gastric cancer tissues. Several studies have shown a significant correlation between serum HER2 levels and tissue HER2 expression [21][22][23]. However, in our study, serum HER2 levels ranged from undetectable to extremely high, even though our cohort was limited to patients with high-HER2-expressing tumors.…”

Section: Discussionmentioning

confidence: 63%

See 1 more Smart Citation

Five-weekly S-1 plus cisplatin therapy combined with trastuzumab therapy in HER2-positive gastric cancer: a phase II trial and biomarker study (WJOG7212G)

et al. 2017

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Section: Discussioncontrasting

confidence: 74%

Section: Discussionmentioning

confidence: 63%

Five-weekly S-1 plus cisplatin therapy combined with trastuzumab therapy in HER2-positive gastric cancer: a phase II trial and biomarker study (WJOG7212G)

et al. 2017

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“…These results suggest that serum HER2 level elevates when HER2-positive breast cancer metastasizes to distant organs. To the best of our knowledge, only seven studies [16][17][18][19][20][21][22] to date have investigated the serum HER2 level in gastric cancer and results were conflicting like breast cancer: five studies [16,[19][20][21][22]] demonstrated significant correlation between serum and tissue HER2 levels while two [17,18] did not. Similar to the condition of breast cancer studies, the latter included only 13% [17] or no [18] metastatic gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Serum HER2 as an adjunct to assess HER2 status for advanced gastric cancer: A prospective multicenter trial (SHERLOCK)

et al. 2016

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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 ¼ 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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“…Generally, high serum HER2 ECD levels in patients with metastatic breast cancer were correlated with high risk of disease progression, decreased survival, and reduced response to treatment[11-13]. Several studies have also investigated the clinical significance of serum HER2 ECD in gastric cancer[14-16]. However, differences in detection methods and patient enrollment across studies have led to inconsistent results regarding the associations among serum HER2 ECD concentrations, tissue HER2 status, and patient outcome.…”

Section: Introductionmentioning

confidence: 99%

Serum HER2 as a predictive biomarker for tissue HER2 status and prognosis in patients with gastric cancer

Shi¹,

Wang²,

Huang³

et al. 2017

WJG

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AIMTo investigate the association between serum human epidermal growth factor receptor 2 (HER2) extracellular domain (ECD) and tissue HER2 status, and the prognostic value of serum HER2 ECD in patients with gastric cancer.METHODSA total of 239 patients with gastric cancer were enrolled from December 2012 to June 2013. Serum HER2 ECD was determined by chemiluminescent assay, and tissue HER2 status was evaluated by immunohistochemistry and fluorescence in situ hybridization assay. A receiver operating characteristic (ROC) curve was plotted to identify the optimal cut-off value for serum HER2 ECD assay for predicting survival in gastric cancer patients.RESULTSSerum HER2 ECD was significantly correlated with tissue HER2 status (P < 0.001), tumor size (P < 0.001), and intestinal type of gastric cancer (P = 0.021). Serum HER2 ECD levels differed significantly between patients with HER2-positive tissue expression and those with HER2-negative tissue expression. ROC analysis yielded an area under the curve value of 0.79 (95%CI: 0.71-0.87, P < 0.001), with a sensitivity and specificity of 0.54 (95%CI: 0.37-0.70) and 0.93 (95%CI: 0.88-0.96), respectively. With a cut-off value of 24.75 ng/mL, high serum HER2 ECD had a negative impact on overall survival of the patients (HR: 1.93, 95%CI: 1.32-4.38, P = 0.006).CONCLUSIONSerum HER2 ECD could be a highly specific surrogate biomarker for tissue HER2 status in gastric cancer. Optimal cut-off criteria for predicting survival should be established.

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Serum HER2 Extracellular Domain as a Potential Alternative for Tissue HER2 Status in Metastatic Gastric Cancer Patients

Abstract: Levels of serum HER2 ECD are highly correlated with tissue HER2 status in metastatic gastric cancer. Serum HER2 ECD assay can be considered as a potential alternative for tissue HER2 status.

Cited by 15 publications

References 22 publications

Five-weekly S-1 plus cisplatin therapy combined with trastuzumab therapy in HER2-positive gastric cancer: a phase II trial and biomarker study (WJOG7212G)

Five-weekly S-1 plus cisplatin therapy combined with trastuzumab therapy in HER2-positive gastric cancer: a phase II trial and biomarker study (WJOG7212G)

Serum HER2 as an adjunct to assess HER2 status for advanced gastric cancer: A prospective multicenter trial (SHERLOCK)

Serum HER2 as a predictive biomarker for tissue HER2 status and prognosis in patients with gastric cancer

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