Circulating CEA-positive and EpCAM-negative tumor cells might be a predictive biomarker for recurrence in patients with gastric cancer

循环 CEA 阳性和 EpCAM 阴性肿瘤细胞可能是胃癌患者复发的预测生物标志物

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作者:Yuichiro Miki, Masakazu Yashiro, Kenji Kuroda, Tomohisa Okuno, Shingo Togano, Go Masuda, Hiroaki Kasashima, Masaichi Ohira

Abstract

It has been reported that circulating tumor cells (CTCs) are beneficial for predicting tumor stage or treatment response. Although epithelial cell adhesion molecules (EpCAMs) and cytokeratin (CK) have been often used for the identification of CTCs, other tumor markers have not been fully investigated as detecting tools for CTCs. Thus, this study aims to clarify the significance of carcinoembryonic antigen (CEA, CD66e)-positive CTCs in patients with gastric cancer. A total of 150 patients with gastric cancer were enrolled in this study. The mononuclear fraction of peripheral blood was enriched by Ficoll. The number of cells was enumerated depending on the positivity of EpCAM and CEA or CK by flow cytometry. The association of these cells with clinicopathologic characteristics was investigated. The mean age was 70 (range 28-92). The macroscopic type of gastric cancer was classified as 0/1/2/3/4/5 in 59/11/22/38/16/4 patients, respectively. Seventy-one patients (47.3%) were diagnosed with intestinal-type cancer, while 76 patients (50.7%) were diagnosed with the diffuse type. The mean numbers of cells with EpCAM-CK+, EpCAM+CK-, EpCAM+CK+, EpCAM-CEA+, EpCAM+CEA-, and EpCAM+CEA+ were 618, 237, 19.9, 1147, 291, and 7.41, respectively. The number of EpCAM-CEA+cells was significantly higher in patients with stage II-III and IV than in patients with stage I. The 3-year RFS rate in patients with a high number of EpCAM-CEA+cells (>=622) was 57.5%, while it was 79.3% in patients with a low number of EpCAM-CEA+cells (<622) (log-rank p = 0.0079). Thus, we conclude that CEA-positive CTCs will be a clinically beneficial biomarker in patients with gastric cancer.

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