Journal Article

Monitoring the HER2 copy number status in circulating tumor DNA by droplet digital PCR in patients with gastric cancer

Shoda, Katsutoshi, Komatsu, Shuhei, Ichikawa, Daisuke, Konishi, Hirotaka, Taniguchi, Hiroki, Kakihara, Naoki, Okamoto, Kazuma, Fujita, Yuji, Arita, Tomohiro, Shiozaki, Atsushi, Masuda, Kiyoshi, Hiramoto, Hidekazu, Otsuji, Eigo, Hamada, Junichi, Imoto, Issei

2017

Overview

Background We previously demonstrated the potential of circulating tumor DNA (ctDNA) for the amplification of detecting HER2 in patients with gastric cancer (GC). In the present study, we focused on the clinical courses of patients who developed recurrence with GC, and investigated the potential clinical utility of the ddPCR-based HER2 copy number (CN) as a marker for the temporal and/or spatial heterogeneities of GC during treatment progress. Method We enrolled 30 healthy volunteers and 60 patients with GC who underwent surgery, including 17 patients who developed recurrence. Using ribonuclease P RNA component H1 ( RPPH1 ) as a reference gene, plasma HER2 to RPPH1 ratios (the HER2 ratio) were determined using ddPCR. Results The preoperative plasma HER2 ratio correlated with the tumor HER2 status ( p  < 0.001), and sensitivity and specificity were 0.733 and 0.933, respectively. Analyses of plasma samples during the postoperative follow-up periods revealed that high plasma HER2 ratios were detected at the time of recurrence in 7 of 13 cases, which were diagnosed as being HER2 negative at the time of surgery. These results were supported by continuously increasing HER2 ratios thereafter with the progression of recurrent cancer. Conclusion The plasma HER2 ratio determined by ddPCR is a repeatable and noninvasive approach for real-time evaluations of the HER2 status to monitor the effects of treatments for patients with HER2-positive GC and enable treatment options for patients with HER2-negative GC but positive conversion of the HER2 status after recurrence.

• Publisher: Springer Japan,Springer Nature B.V
• Subject: Abdominal Surgery / Adenocarcinoma - blood / Adenocarcinoma - genetics / Adenocarcinoma - secondary / Aged / Aged, 80 and over / Biomarkers, Tumor - blood / Biomarkers, Tumor - genetics / Cancer Research / Case-Control Studies / DNA Copy Number Variations - genetics / DNA, Neoplasm - blood / DNA, Neoplasm - genetics / Female / Follow-Up Studies / Gastric cancer / Gastroenterology / Humans / Lymphatic Metastasis / Male / Medicine / Medicine & Public Health / Middle Aged / Neoplasm Invasiveness / Neoplasm Staging / Oncology / Original Article / Peritoneal Neoplasms - blood / Peritoneal Neoplasms - genetics / Peritoneal Neoplasms - secondary / Prognosis / Real-Time Polymerase Chain Reaction - methods / Receptor, ErbB-2 - blood / Receptor, ErbB-2 - genetics / Stomach Neoplasms - blood / Stomach Neoplasms - genetics / Stomach Neoplasms - pathology / Surgical Oncology