Molecular genetics and targeted therapeutics in biliary tract carcinoma

Table 2 Frequency of mutation or abnormal expression of molecular targets in biliary tract carcinoma

Target	Type of alteration	GBC	EHCC	IHCC	Ref.
Growth factors/receptors
EGFR	Point mutation	6%-9%	14%-20%	3%-20%	[29,84]
EGFR	Increased expression	12%	5%-19%	11%-27%	[28,93]
HER2	Increased expression	16%	5%-8%	0%-1%	[28,93]
MET	Increased expression	5%-74%	0%	21%-58%	[93,94]
VEGF	Increased expression	55%-63%	59%	53%	[28,34]
RAS/RAF/MEK pathway
KRAS	Point mutation	0-13%	0%-23%	5%-54%	[29,39,95-99,101]
BRAF	Point mutation	0-33%	0%-2%	0%-21%	[29,39-41,101]
MEK	-	Unknown	Unknown	Unknown	-
PI3K/AKT/mTOR pathway
PI3K/PIK3CA	Point mutation	4%-12%	0	0%-9%	[45,99-101]
AKT	Point mutation	0	0	0-3	[101,102]
mTOR	Increased activation	47%-64%	65%	70%	[50,103]

AKT: Protein kinase B; BRAF: Proto-oncogene BRAF; EGFR: Epithelial growth factor receptor; EHCC: Extrahepatic cholangiocarcinoma; GBC: Gallbladder carcinoma; HER2: Human epidermal growth factor receptor 2; IHCC: Intrahepatic cholangiocarcinoma; KRAS: Kirsten rat sarcoma viral oncogene homolog; MET: Hepatocyte growth factor receptor; MAPK: Mitogen activated protein kinase; MEK: MAPK kinase; mTOR: Mammalian target of rapamycin; PI3K: Phosphoinositide 3-kinase; VEGF: Vascular endothelial growth factor.