Liquid biopsy in patients with pancreatic cancer: Circulating tumor cells and cell-free nucleic acids

Table 1 Circulating tumor cells in pancreatic cancer

Ref.	Patient characteristics	Number of patients with PCa	Controls	Enrichment/isolation method	Detection method	Detection rate
Funaki et al[28], 1996	Pre- or post-treatment	9	NA	None	RT-PCR: CEA mRNA	33.3% of PCa
Funaki et al[29], 1998	Preoperative	3	NA	None	RT-PCR: CEA-mRNA
Miyazono et al[30], 1999	Intra-operative	21	15 HV	Density gradient enrichment	RT-PCR: CEA-mRNA	61.9% of PCa
Chausovsky et al[33], 1999	Metastatic PCa	28	22 BD	Density gradient enrichment	RT-PCR: CK20 mRNA	78.6% of PCa
Z'graggen et al[124], 2001	All stages, preoperative	105	66 HV	Density gradient enrichment	ICC: CK-AE1/AE3	Sensitivity: 26%, specificity: 96%
Lukyanchuk et al[34], 2003	NA	11	18 HV	Density gradient enrichment	RT-PCR: CK-20 and PSCA	CK-20: 19 of 47 (40.4%), PSCA: 22 of 47 (46.8%)
Clarke et al[37], 2003	NA	11	23 HV	Density gradient enrichment	RT-PCR: EGFR mRNA	18% of PCa, 0.0% of HV
Mataki et al[32], 2004	All stages	20	15 HV, 15 BD	Density gradient enrichment	RT-PCR: CEA mRNA	Sensitivity: 75.0%, specificity: 94.6%
Zhang et al[35], 2005	Stages II and III	40	5 BD, 5 HV	Not available	RT-PCR: CK20 mRNA	57.5% of PCa
Soeth et al[36], 2005	Preoperative	154	NA	Density gradient enrichment	RT-PCR: CK20 mRNA	33.8% of PCa
Ishizone et al[38], 2006	All stages	55	10 CP, 70 HV	Density gradient enrichment	RT-PCR: a4GnT	76.4% of PCa, 40.0% of CP, 17.1% of HV
Hoffmann et al[39], 2007	All stages	37	16 CP, 15 BD	Density gradient enrichment	RT-PCR: CK-19 mRNA	64% of PCa
Kurihara et al[41], 2008	Stages II, III and IV	26	11 CP, 10 HV	CELLSEARCH®		42% of PCa
Zhou et al[40], 2011	All stages	25	15 BD	Immunomagnetic separation	RT-PCR: C-MET, h-TERT, CK20, and CEA	Sensitivity: 100%, specificity: 93.3%
Khoja et al[125], 2012	Stages III and IV	54 PCa	NA	Size-based selection	RT-PCR: EpCAM, CK, vimentin, and CEA	ISET 49/54 (93%) vs CELLSEARCH® 21/54 (40%)
de Albuquerque et al[126], 2012	Stages III and IV	34	40 HV	Immunomagnetic separation	RT-PCR: KRT19, MUC1, EpCAM, CEACAM5, and BIRC5	Sensitivity: 47.1%, specificity: 100%
Kamande et al[127], 2013	All stages	12	5 HV	Microfluidic; ICC	DAPI+, CD45-, CK+	100% of PCa
Bidard et al[42], 2013	Locally advanced PCa	79	NA	CELLSEARCH®		11% of PCa
Iwanicki-Caron et al[43], 2013	All stages	40	NA	Size-based selection	Cell size and cytopathologic criteria	Sensitivity: 55.5%, specificity: 100%, accuracy: 70%
Bobek et al[45], 2014	All stages	24	NA	Size-based selection	DAPI, CK, CEA, vimentin IHC	66.7% of PCa
Sheng et al[48], 2014	Metastatic PCa	18	NA	Multifluidic, "GEM"Chip		94.4% of PCa
Rhim et al[47], 2014	All stages	11	19 HV	Geometrically enhanced differential immunocapture	ICC for DAPI, CD45, CK, and PDX-1	73% of PCa
Catenacci et al[128], 2015	Stages II, III and IV	18	NA	Immune-magnetic separation	CD45-negative and positive for CK8, -18, and/or -19 and DAPI	118.4 ± 36.8 CTCs/7.5 mL PVB, compared with a mean of 0.8 ± 0.4 CTCs/7.5 mL PB
Earl et al[81], 2015	All stages	35	NA	CELLSEARCH®		20% of PCa
Cauley et al[44], 2015	All stages	105	9 HV	Size-based selection	Cytomorphologic criteria	48.6% of PCa
Kulemann et al[46], 2015	Preoperative	11	9 HV	Size-based selection: ScreenCell	Cytologic and detection of KRAS mutation	75% of early PCa, 71.4% of advanced PCa
Zhang et al[129], 2015	All stages	32	30 HV	ICC and FISH	DAPI+, CD45-, and CK+, or CEP8 > 2+	Sensitivity: 63.6%, specificity: 94.4%
Bissolati et al[130], 2015	Intra-operative	20	NA	CELLSEARCH®		PVB: 40%, PB: 20%
Zhang et al[131], 2015		15	15 HV	Immunomagnetic separation	BC-15 aptamer or anti-CK staining	73.3% of PCa

BD: Benign disease; CEA: Carcinoembryonic antigen; CK: Cytokeratin; CP: Chronic pancreatitis; CTC: Circulating tumor cell; DAPI: 4′,6′-diamidino-2-phenylindole; EpCAM: Epithelial cellular adhesion molecule; FISH: Fluorescence in situ hybridization; HV: Healthy volunteer; ICC: Immunocytochemistry; IHC: Immunohistochemistry; NA: Not applicable; PB: Peripheral blood; PCa: Pancreatic cancer; PVB: Portal venous blood; RT-PCR: Reverse transcription polymerase chain reaction.