Genomic and genetic alterations influence the progression of gastric cancer

Table 1 Molecular genetic changes in gastric cancer

	Abnormalities	Intestinal phenotype (%)	Diffuse phenotype (%)	Local progression	Distant metastasis	Prognosis	Prolonged survival	Ref.
Microsatellite instability	Mutation, hypermethylation, reduced expression	20-30	0-10	No	NA	Good	Yes	[8,11]
Tyrosine kinases
HER2/neu	Amplification/overexpression	10-15	0	Yes	Yes	Poor	No	[57-59]
RUNX3	Hemizygous deletion/hypermethylation/loss of expression	15-45	40-80	Yes	Yes	Poor	No	[62-64]
FHIT	Loss of protein expression (LOH, MSI)	35-65	20-80	Yes	Yes	Poor	No	[65,66]
NM23	Downregulation	3-25	30-70	Yes	Yes	Poor	Discordant results	[73,75]
VEGF	Overexpression	65	35-45	Yes	Yes	Poor	No	[77-79]
HIF-1α	Overexpression	25-60	45-60	Discordant results	NA	NA	Discordant results	[80-82]
COX2	Overexpression	60-70	30-70	Yes	Yes	Discordant results	No	[77,83,84]
SPARC	Overexpression	70-80	25-55	Discordant results	Yes	Poor	No	[85-87]
p53	LOH/mutation/hypermethylation/overexpression	20-40	20-40	Yes	Yes	No correlation	No	[88-91]
p21	Loss	60		Yes	Yes	Poor	No	[92-94]
p27	Reduced expression	50		Yes	Yes	Poor	No	[95-97]
bcl2	LOH/overexpression	40	0	No	No	Good	Yes	[98]
BAX	Reduced expression	10	5	NA	Yes	Poor	No	[99]
pRb	Reduced expression	60	50	NA	NA	Poor	No	[1,92]
c-myc	Overexpression	45	10	Possible	Possible	Poor	No	[101-104]
	Amplification	15	5	Possible	Possible	Poor	No
Cyclin E	Amplification/overexpression	15-20		Yes	Yes	Poor	No	[92]
E-cadherin	LOH/mutation/hypermethylation/reduced expression	0	50	Yes	Yes	Poor	No	[107,108]
MUC1	Overexpression	30-60	15-65	Yes	No	Poor	No	[65,106,110]
PRL-3	Overexpression	30-40	25-60	Yes	Discordant results	Poor	No	[112-114]
Tumor-associated proteases								[115-117]
PAI-1	Overexpression	45-75	35-50	Yes	Yes	Poor	No
uPAR	Overexpression	40-75	30-50	Yes	NA	Poor	No
uPA	Overexpression	65	30	Yes	NA	Poor	No

FHIT: Fragile histidine triad; LOH: Loss of heterozygosity; MSI: Microsatellite instability; VEGF: Vascular endothelial growth factor; HIF-1α: Hypoxia inducible factor-1α; COX2: Cyclooxygenase-2; SPARC: Secreted protein acidic and rich in cysteine; PRL-3: Phosphatase regenerating liver 3; PAI-1: Plasminogen activator inhibitor type I; uPA: Urokinase-type plasminogen activator; u-PAR: u-PA receptor; NA: Not available.