Diagnostic and therapeutic biomarkers in pancreaticobiliary malignancy

Table 2 Tissue-based diagnostic biomarkers for cholangiocarcinoma

	Diagnostic marker	Countries	Total patients, n	CCA patients, n	Sensitivity (%)	Specificity (%)
PSC-associated strictures	Brush Cytology[21,76,134-140]	United States, The Netherlands, Sweden, Norway	828	138	7-73	89-100
	FISH polysomy[21,73,136,137,140]	United States	387	89	22-50	88-100
	FISH polysomy or trisomy[21,73,136,140]	United States	373	75	60-88	57-87
	Kras[141,142]	Norway, United States	180	74	29-47	96-100
	p53[142]	Norway	48	33	31	100
	Cytology + CA19-9[135]	United States	333	44	87.5	97.3
	Cytology + DNA aneuploidy + CA19-9 + CEA[138]	Sweden	20	7	88-100	80-85
	Cytology + p53 + KRAS[76]	The Netherlands	23	10	100	79
	FISH + KRAS[141]	United States	14	14	50-68	96
Indeterminate strictures	Brush Cytology[75,78,79,136,140,143-150]	United States, Germany, France, Italy	640	199	5.8-80	92-100
	FISH Polysomy[75,78,79,136,137,140]	United States, Italy	386	165	31-80	97-100.0
	FISH Polysomy or trisomy[75,136,140]	United States	147	88	49-64	79.6-100
	Biopsy[144,145,147,150-153]	United States, Japan, France	347	65	30-88	97-100
	FNA[145,154]	United States	133	30	25-61.6	100.0
	Cytology + biopsy[144,150]	France, Austria	258	28	63-86	97-100
	Cytology + FNA + biopsy[145]	United States	133	30	47-52	100
	Cytology + KRAS[155]	Belgium	142	12	55	100

Some studies included all biliary tract cancers (cholangiocarcinoma, gallbladder, pancreatic and ampullary), but sensitivity and specificity values were similar, so data is merged. Endobiliary sampling technique for cytology and FISH: ERCP or PTC brushing; Biopsy technique: Standard forceps, mini-forceps or transpapillary biopsy. FISH: Fluorescent in situ hybridization; PTC: Percutaneous transhepatic cholangiography; CCA: Cholangiocarcinoma; PSC: Primary sclerosing cholangitis; p53: Tumor protein p53; KRAS: Kirsten rat sarcoma viral oncogene homolog; CEA: Carcinoembryonic antigen; CA 19-9: Cancer antigen 19-9; FNA: Fine-needle aspiration.