In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 5592-5592
Abstract:
In around 10% of gastric cancer, amplification and overexpression of the human epidermal growth factor receptor 2 (HER2) is observed and trastuzumab is adopted as a target therapy agent for HER2-positive gastric cancer. Because of efficiency and accuracy, droplet digital PCR (ddPCR) is one of the best methods for measuring HER2 amplification, especially in cell-free plasma samples. In this study, we aimed to investigate the correlation between tissue and plasma HER2 status by using ddPCR method in gastric cancer patients. We collected formalin-fixed and paraffin-embedded tissue (FFPE) and cell-free plasma samples of 81 gastric cancer patients, including 30 HER2 immunohistochemistry (IHC)-negative (0 or 1+) cases and 51 HER2 IHC-positive cases (IHC 2+, n=20; IHC 3+, n=31), with informed consents. We performed ddPCR of a target gene HER2 and a reference gene EIF2C1 in both tissue and cell-free plasma samples, and gene copy number (GCN) of HER2 was calculated. The median HER2 GCN of tissue DNA ddPCR was 2.61 (1.47-49.00) and the median GCN of plasma ddPCR was 1.83 (0.97-7.67). HER2 IHC results showed moderate correlation with HER2 GCN of tissue ddPCR (r=0.455, p & lt;0.001) and weak correlation with plasma ddPCR (r=0.321, p=0.003). A ratio & gt;2.405, which showed the best discriminating level from a receiver operating characteristic curve, was defined as a cut-off for tissue HER2 amplification using ddPCR method. Comparing the HER2 amplification results of tissue DNA ddPCR to HER2 IHC results, the concordance rate was 86.4% with Cohen's kappa of 0.715. Sensitivity and specificity of tissue ddPCR were 86.3% and 86.7%, respectively. HER2 amplification by tissue ddPCR was significantly associated with advanced gastric cancer and lymphatic invasion (p & lt;0.05). HER2 GCN of tissue ddPCR was weakly correlated with plasma ddPCR (r=0.250, p=0.025). Sensitivity and specificity of plasma ddPCR for HER2 IHC positivity were 35.3% and 93.3%, respectively. However, sensitivity and specificity of plasma ddPCR were 66.7% and 60.0% with another cut-off of 1.715. In 51 HER2 IHC-positive cases, intratumoral heterogeneity was observed in 100% (5/5) of both tissue and plasma ddPCR-negative cases, 100% (2/2) of tissue-negative and plasma positive cases, 64.3% (18/28) of tissue-positive and plasma-negative cases, and 50.0% (8/16) of both positive cases (p=0.026). In conclusion, HER2 GCN of plasma ddPCR showed a weak correlation with tissue ddPCR, and the sensitivity of plasma ddPCR was not high. Intratumoral heterogeneity is suggested to be one of the possible causes, and these findings may contribute to developing plasma HER2 testing useful in daily practice. Citation Format: Boram Kim, Soo Kyung Nam, Soo Hyun Seo, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Kyoung Un Park, Hye Seoung Lee. HER-2 copy number measurement in tissue and cell-free plasma DNA of gastric cancer patients using droplet digital PCR method [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5592.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2018-5592
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2018
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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