Surgical Maneuvers Enhance Molecular Detection of Circulating Tumor Cells During Gastric Cancer Surgery

Miyazono, Futoshi; Natsugoe, Shoji; Takao, Sonshin; Tokuda, Koki; Kijima, Fumio; Aridome, Kuniaki; Hokita, Shuichi; Baba, Masamichi; Eizuru, Yoshito; Aikou, Takashi

doi:10.1097/00000658-200102000-00007

Cited by 96 publications

(65 citation statements)

References 18 publications

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“…(14)(15)(16)(17)(18) We reported that the presence of CTC correlates with tumor progression and outcomes of patients with esophageal, gastric and biliary-pancreatic cancer.…”

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confidence: 99%

“…(12,13) The RT-PCR is a useful assay for detecting circulating tumor cells (CTC) within blood specimens from patients with various malignancies, including gastric cancer. (14)(15)(16)(17)(18) We reported that the presence of CTC correlates with tumor progression and outcomes of patients with esophageal, gastric and biliary-pancreatic cancer.(14-18) Several epithelial-specific antigens such as CEA, cytokeratin-19, and cytokeratin-20, have been used generally in many studies of CTC detection in gastric cancer. (15,19) However, recent studies have found false-positive results in RT-PCR assays using these markers for CTC detection.…”

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confidence: 99%

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B7‐H3 expression in gastric cancer: A novel molecular blood marker for detecting circulating tumor cells

et al. 2011

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The clinical significance of B7-H3 expression in gastric cancer remains unclear, although the B7 ligand family plays a critical role in the T cell-mediated immune response. We therefore investigated B7-H3 expression as a blood marker of circulating tumor cells and determined correlations with tumor progression in patients with gastric cancer. B7-H3 expression in gastric cell lines was initially evaluated by immunocytochemistry. Furthermore, we used quantitative RT-PCR to assess B7-H3 mRNA expression in four cell lines and in 95 blood specimens from patients with gastric cancer, as well as in 21 samples of peripheral blood lymphocytes from healthy volunteers. B7-H3 expression in cell lines was identified by immunocytochemistry and quantitative RT-PCR. Blood specimens from patients with gastric cancer contained significantly more copies of B7-H3 mRNA than those from healthy volunteers without cancer (P < 0.0001). Levels of B7-H3 expression significantly correlated with overall stage (P = 0.013). The 5-year survival rate was significantly lower in patients with high B7-H3 expression than with low expression (P = 0.02). Multivariate analysis demonstrated that B7-H3 expression was an independent prognostic factor (P = 0.046). Our results indicate that B7-H3 appears to be a useful blood marker for predicting tumor progression in gastric cancer. (Cancer Sci 2011; 102: 1019-1024 G astric cancer is one of the most common gastrointestinal tract malignancies in Asia.(1-4) New anticancer agents such as S-1, taxanes, capecitabine, irinotecan and oxaliplatin have improved the prognosis of patients with unresectable advanced gastric cancer.(5-9) Nevertheless, the 5-year survival rates of patients with International Union Against Cancer (UICC) stage IIIA, IIIB, and IV gastric cancers are 30.8-54.0%, 16.1-36.5% and 9.2-23.9%, respectively.(10,11) Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are commonly used as established tumor markers in blood for patients with gastric cancer. However, the sensitivity and specificity of predicting tumor progression and postoperative recurrence are clinically insufficient and no molecular biomarkers can yet predict the prognosis of patients with gastric cancer. (12,13) The RT-PCR is a useful assay for detecting circulating tumor cells (CTC) within blood specimens from patients with various malignancies, including gastric cancer. (14)(15)(16)(17)(18) We reported that the presence of CTC correlates with tumor progression and outcomes of patients with esophageal, gastric and biliary-pancreatic cancer.(14-18) Several epithelial-specific antigens such as CEA, cytokeratin-19, and cytokeratin-20, have been used generally in many studies of CTC detection in gastric cancer. (15,19) However, recent studies have found false-positive results in RT-PCR assays using these markers for CTC detection. (20,21) Consequently, RT-PCR assays using conventional CTC markers have low specificity for detecting occult CTC from blood specimens. Furthermore, few candidate molecular blood markers of...

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“…(14)(15)(16)(17)(18) We reported that the presence of CTC correlates with tumor progression and outcomes of patients with esophageal, gastric and biliary-pancreatic cancer.…”

mentioning

confidence: 99%

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confidence: 99%

B7‐H3 expression in gastric cancer: A novel molecular blood marker for detecting circulating tumor cells

et al. 2011

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“…16‐34 The gap observed in the incidence of CTC among each study may be as a result of differences in the clinicopathological backgrounds of enrolled patients, target markers, blood volumes assessed by PCR, and the cut‐off values for mRNA levels. However, the incidence of CTC ranged between 36.6% and 52.2% in five RT‐PCR studies targeting CEA, which is one of the conventional PCR markers for the detection of CTC 17, 18, 19, 21, 29. According to studies assessed in this review article, positive rates of serum CEA ranged between 24.3% and 26.3% 21, 29, 31.…”

Section: Incidence Of Ctcmentioning

confidence: 89%

“…reported that the positive rates for CEA mRNA expression before and after gastrectomy were 8.8% (5/57) and 33.3% (19/57), respectively 17. Moreover, they demonstrated a close relationship between the presence or absence of CEA mRNA expression and disease recurrence, such as liver metastases 17. The findings of this study suggest that surgical maneuvers enhance the metastatic process from the detachment of primary tumor cells into the systemic circulation in patients with gastric cancer.…”

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confidence: 99%

Clinical significance of circulating tumor cells in blood from patients with gastric cancer

Arigami

Uenosono

Yanagita

et al. 2017

Annals of Gastroent Surgery

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Circulating tumor cells (CTC) have been focused on as a target for detecting occult tumors, predicting therapeutic responses and prognoses, and monitoring postoperative recurrence in the clinical management of patients with various malignancies, including gastric cancer. Recent advances in molecular diagnostic tools have contributed to high sensitivity and specificity for the detection of CTC. A conspicuous disparity exists in the incidence of CTC among studies. However, a close relationship has been reported between positivity for CTC and well‐known prognostic clinicopathological factors including depth of tumor invasion, lymph node metastasis, stage, and lymphatic and venous invasion in patients with gastric cancer. According to most studies published on the clinical impact of CTC, the presence of CTC negatively affects the prognosis of patients with gastric cancer. Moreover, the study of CTC based on a meta‐analysis demonstrated their importance as a poor prognostic indicator. In clinical management, pre‐ and post‐therapeutic monitoring of CTC using liquid biopsy may be useful for early detection of subclinical patients or disease recurrence, prediction of tumor progression, and administrative control of adjuvant chemotherapy. Although their functional properties remain unclear, molecular profiling of CTC may contribute to the development of personalized treatment that effectively inhibits tumor progression in patients with advanced gastric cancer. We herein review the clinical significance of CTC as a promising blood marker and therapeutic target in patients with gastric cancer.

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“…Concomitant molecular analysis for CTCs with a multimarker panel is justifiable supplementary approaches to current pathological staging system, which may help physicians make accurate judgment on clinical treatments and predicting prognosis for GC patients. The high false positive rate (43.5%) of membrane array in the prediction of postoperative recurrence/metastasis, at least in part, might result from the timing of blood sampling during surgical procedures, 37 which probably enhanced the relief of CTCs. A blood sampling procedure carried out before or after operation can be a resolution to overcome such a problem.…”

Section: Discussionmentioning

confidence: 99%

Development of a high‐throughput membrane‐array method for molecular diagnosis of circulating tumor cells in patients with gastric cancers

Lin

et al. 2006

Intl Journal of Cancer

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Recently several noninvasive methods have been employed to detect circulating tumor cells (CTCs) in cancer patients. In this study, we have developed a highly sensitive, high-throughput colorimetric membrane-array method that was designed to detect a panel of mRNA markers including human telomerase reverse transcriptase (hTERT), , carcinoembryonic antigen (CEA) and mucin 1 (MUC1) mRNA for the presence of CTCs in the peripheral blood of patients with gastric cancer (GC). Digoxigenin-labeled cDNA targets synthesized following total RNA isolation from peripheral blood samples of 64 GC patients and 80 healthy individuals were subjected to membrane-array hybridization. The results showed that membrane array could positively detect 5 cancer cells/ml of peripheral blood in GC cell-dilution experiments. The sensitivity, specificity and diagnostic accuracy for hTERT, CK-19, CEA and MUC1 mRNA ranged from 78.1% to 82.8%, 76.3% to 85% and 81.3% to 83.3%, respectively. Both CEA and MUC1 mRNA expression was correlated significantly with all malignant biological properties of GC, such as macroscopic type, depth of tumor invasion, lymph-node metastasis, TNM stage and coexisting distant metastasis (all p < 0.05). Using these 4 markers in combination, the sensitivity, specificity and diagnostic accuracy of membrane array were raised to 89.1%, 91.3% and 90.3%, respectively. The expression of all 4 mRNA markers was an independent predictor for postoperative recurrence/metastasis. GC patients with the expression of all the 4 mRNA markers showed a poorer survival rate than those without the expression of any 1 mRNA marker (p 5 0.0223). These findings demonstrated that our membrane-array method could detect CTCs in the circulation of GC patients with considerably high sensitivity and specificity. The identification of CTCs in the peripheral blood may be useful in the auxiliary cancer diagnostics or postoperative surveillance of GC patients for recurrence/metastasis. ' 2006 Wiley-Liss, Inc.Key words: circulating tumor cell; membrane array; gastric cancer; molecular diagnosisThe degrees of tumor penetration in the stomach wall and lymph node metastasis have been used for many decades as the 2 major prognostic determinants for gastric cancer (GC) patients. Unfortunately, despite informative staging of patients with GC, some patients with apparently localized disease at diagnosis will subsequently develop recurrent or metastatic diseases. 1-4 One of the major causes is attributed to the presence of disseminated tumor cells shed from the primary carcinoma into circulation, prior to or during surgery. Even in patients with early GC, blood-born metastasis occurs. 2,5,6 Recent attempts to improve staging include sensitive detection of disseminated tumor cells in the blood or lymph nodes by molecular approaches. Evidence increasingly clarifies that primary cancers begin shedding neoplastic cells into the circulation at an early stage. [7][8][9] It is the dissemination of cancer cells into circulation that is widely accepted as the main cause l...

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Surgical Maneuvers Enhance Molecular Detection of Circulating Tumor Cells During Gastric Cancer Surgery

Cited by 96 publications

References 18 publications

B7‐H3 expression in gastric cancer: A novel molecular blood marker for detecting circulating tumor cells

B7‐H3 expression in gastric cancer: A novel molecular blood marker for detecting circulating tumor cells

Clinical significance of circulating tumor cells in blood from patients with gastric cancer

Development of a high‐throughput membrane‐array method for molecular diagnosis of circulating tumor cells in patients with gastric cancers

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