| Affected Protein |
Pathway |
Sub-Type |
Ethnicity |
Stage |
Frequency (%) |
Gene Amplification |
Activating Mutation |
Inactivating Mutation |
Deletion |
Promoter Hypermethylation |
Comment |
|
|
APC (adenomatosis polyposis coli) |
WNT Signaling
|
intestinal type |
|
|
60% |
|
|
|
|
|
rare in diffuse type |
|
|
BCL-2 |
Apoptosis regulation
|
|
|
|
12-35% |
|
|
|
|
|
LOH/ overexpression. Negative correlation of expression with depth of invasion, lymph node metastasis and survival |
|
|
beta-catenin |
WNT Signaling
|
intestinal |
|
|
27% |
|
|
|
|
|
|
|
|
c-Met (HGFR) |
Receptor Tyrosine Kinase Signaling
|
diffuse type |
|
|
40% |
|
|
|
|
|
Correlation with tumor invasion, lymph node metastasis, poor prognosis |
|
|
c-Met (HGFR) |
Receptor Tyrosine Kinase Signaling
|
intestinal type |
|
|
20% |
|
|
|
|
|
overexpression |
|
|
C-Myc |
Cell Cycle Regulation
|
|
|
|
40-45% |
|
|
|
|
|
Correlation with poor clinical course/predictor of aggressiveness |
|
|
CDKN1B (p27, Kip1) |
Cell Cycle Regulation
|
|
|
|
40-50% |
|
|
|
|
|
Reduced expression. Correlation with advanced tumor stage/depth of invasion/lymph node metastasis |
|
|
Cyclin E1 |
Cell Cycle Regulation
|
diffuse and intestinal, respectively |
|
|
10-20% |
|
|
|
|
|
Overexpression. Correlation with disease aggressiveness/lymph node metastasis |
|
|
E-Cadherin (CDH1) |
Cell-cell adhesion
|
Hereditary Diffuse Gastric Carcinoma (HDGC) |
|
|
50% |
|
|
|
|
|
|
|
|
E-Cadherin (CDH1) |
Cell-cell adhesion
|
sporadic diffuse-type |
|
|
40 - 83% |
|
|
|
|
|
Correlation of reduced expression with tumor metastatic ability and poor prognosis |
|
|
EGF |
|
diffuse and intestinal, respectively |
|
|
20 - 40% |
|
|
|
|
|
overexpression |
|
|
EGFR (ErbB-1 receptor) |
Receptor Tyrosine Kinase Signaling
|
difuuse and intestinal, respectively |
|
|
25 - 50% |
|
|
|
|
|
overexpression |
|
|
ErbB-2 (Her2/neu) |
Receptor Tyrosine Kinase Signaling
|
intestinal advanced gastric carcinoma |
|
|
10-15% |
|
|
|
|
|
Overexpression. Correlation with advanced tumor stage, lymph node metastasis, liver metastases, poor prognosis |
|
|
FGFR-2 (k-sam) |
Receptor Tyrosine Kinase Signaling
|
diffuse type |
|
advanced tumor stage |
35% |
|
|
|
|
|
Overexpression. Correlation with advanced tumor stage/poor prognosis |
|
|
KRAS |
Ras Signal Transduction Pathway
|
intestinal |
|
|
10% |
|
|
|
|
|
|
|
|
p16INK4a (CDKN2A) |
Cell Cycle Regulation
|
intestinal and diffuse, respectively |
|
|
12-30% |
|
|
|
|
|
Reduced expression. Correlation with tumor invasion/metastasis |
|
|
p53 |
p53 Tumor Suppressor Pathway
|
primary gastric cancer |
|
|
25 - 40% |
|
|
|
|
|
Correlation of expression with proliferative rate/lymph node metastasis/shortened survival |
|
|
Pi3-kinase |
PI3-Kinase Signaling
|
|
|
|
4 - 25% |
|
|
|
|
|
|
|
|
PTEN |
PI3-Kinase Signaling
|
gastric carcinomas |
|
advanced stage |
20- 39% |
|
|
|
|
|
loss of expression |
|
|
RARbeta (retinoid acid receptor, beta) |
Transcriptional regulation
|
|
|
|
60-65% |
|
|
|
|
|
Reduced expression |
|
|
RUNX3 (runt-related transcription factor 3) |
Transcriptional regulation
|
|
|
|
45-65% |
|
|
|
|
|
loss of expression |
|
|
TGF alpha |
|
diffuse and intestinal |
|
|
55-60% |
|
|
|
|
|
overexpression |
|
|
VEGF |
|
diffuse and intestinal, respectively |
|
|
12- 46% |
|
|
|
|
|
overexpression |
|
