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Open Access Highly Accessed Research article

Prognostic impact of detecting viable circulating tumour cells in gastric cancer patients using a telomerase-specific viral agent: a prospective study

Hiroaki Ito1*, Haruhiro Inoue1, Norimasa Sando1, Satoshi Kimura2, Keigo Gohda3, Jun Sato3, Katsuhiro Murakami3, Shun Ito3, Noriko Odaka1, Hitoshi Satodate1 and Shin-ei Kudo1

Author affiliations

1 Digestive Disease Center, Showa University Northern Yokohama Hospital, 35-1 Chigasakichuo, Tsuzuki-ku, Yokohama 224-8503, Japan

2 Department of Laboratory Medicine and Central Clinical Laboratory, Showa University Northern Yokohama Hospital, 35-1 Chigasakichuo, Tsuzuki-ku, Yokohama, 224-8503, Japan

3 Central Research Laboratories, Sysmex Corporation, 4-4-4 Takatsukadai, Nishi-ku, Kobe, 651-2271, Japan

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Citation and License

BMC Cancer 2012, 12:346  doi:10.1186/1471-2407-12-346

Published: 9 August 2012

Abstract

Background

The identification of circulating tumour cells (CTCs) in peripheral blood is a useful approach to estimate prognosis, monitor disease progression, and measure treatment effects in various malignancies. However, clinical relevance of CTCs is controversial. We attempted to detect viable CTCs in the peripheral blood of gastric cancer patients using a telomerase-specific viral agent.

Methods

We took a 7.5-ml blood sample from 65 treatment-negative gastric cancer patients before surgery and 10 healthy volunteers. We detected viable CTCs in the blood samples after incubating them with a telomerase-specific, replication-selective, oncolytic adenoviral agent carrying the green fluorescent protein (GFP) gene (OBP-401). GFP-positive CTCs were defined as having a diameter of at least 7.735 μm; this threshold was determined by receiver operating characteristic curve analysis. GFP-positive cells were counted under a fluorescence microscope.

Results

There was a significant difference in overall survival among the patients with 0–4 and those with ≥5 GFP-positive CTCs in the stage I–IV disease group and stage II–IV advanced disease group. The number of GFP-positive CTCs was not related to cancer stage. Among the pathological findings, the number of GFP-positive CTCs was only significantly related to venous invasion, although there were trends towards more GFP-positive CTCs with disease progression (tumour depth, lymph node metastasis, distant metastasis, lymphatic invasion, and histological type).

Conclusions

There was a significant relationship between the number of GFP-positive CTCs and overall survival in the patients with gastric cancer. The detection of CTCs using OBP-401 may be useful for prognostic evaluation.

Trial registration

University Hospital Medical Information Network in Japan, UMIN000002018.

Keywords:
Circulating tumour cells; Gastric cancer; Telomerase