Supplementary Table 1: Selected reports comparing primary tumors and metastases.
Method/Histology
Microarrays/SAGE
Lung
Lung
Head and Neck
Esophageal
Gastric
Colorectal
Colorectal
Colorectal
Breast
Breast
Breast
Breast
Breast
Breast
Melanoma
FISH
Breast HER2
Breast HER2
Lung EGFR
Genetic alterations
Bladder
Findings
Reference
LCM
Nodal mets overall similar to primary
tumors
Few distinct genes validated: IGFBP7,
PAX5
Differential gene expression between
brain mets and primary tumors
LN mets overall similar to primary
tumors
MTA1 differentially expressed
LCM
Multiple differentially expressed genes;
Validation of SPP-1, CKS2, CCT5,
STMN1, NDUFB9 overexpression and
GJB2 underexpression in LN mets
compared to primary tumors
LCM
Decreased expression of OPCML,
RNASE1, YES1 in LN met compared
to primary tumor
Upregulation COX6C, SERPINB1,
CCL22 in LN
LCM
Validated upregulation of MAP2,
N-WASP, NCAML1 in mets; S3RP
downregulated
Most primary tumors and mets coclustered
No significant differences
79 differentially expressed genes
between primary and LN; Validation of
decreased expression of MMP2, FN,
OSF2, COLXIA1 in LN mets
Differential expression of IGFBP5, FN,
MMP2, cyclin D1, enolase2 between
primary tumor and LN met
Multiple differentially expressed genes
detected between primary and LN met
Primary tumors similar to mets
70 gene prognostic signature in primary
tumors and mets
Multiple genes differentially expressed
between primary and LN met
LCM
47 genes up-regulated in metastases
Hoang et al. (2005)1
7% of primaries and mets discordant
3% of primaries and mets discordant
27% of primaries and mets discordant
Gancberg et al. (2002)15
Gong et al. (2005)16
Italiano et al. (2006)17
4% tumors showed LOH in LN, not in
Jones et al. (2005)18
Kikuchi et al. (2006)2
Roepman et al. (2006)3
Uchikado et al. (2006)4
Wang et al. (2006)5
Yanagawa et al. (2001)6
Koehler et al. (2004)7
Takahashi Y et al. (2006)8
Hao X et al. (2004)9
Hao et al. (2004)9
Zucchi et al. (2004)10
Weigelt et al. (2003)11
Weigelt et al. (2005)12
Suzuki and Tarin13
Jaeger et al. (2007)14
Colorectal
Colorectal
Colorectal
Colon CIN
Hepatocellular
CGH
Colorectal
Colorectal
RNA expression levels
Colorectal
Colorectal
Colorectal
Colorectal
Colorectal
Colorectal
Pancreatic
Protein expression
Breast HER2
Breast
HER2
Breast
Breast
Breast
Breast
HER2
HER2
HER2
HER2
primary 8% showed different patterns
on LOH in distinct LN mets
30% of primary tumors-mets discordant
for Ki-ras mutation status; 7%
discordant for p53.
Distinct MSI at BAT25 locus and
frequency of mutations in TCF4 in
matched primaries and LNs of MSI
cancers; equal frequencies at other loci.
Intratumoral genetic heterogeneity for
p53 and K-ras lost in mets.
Mets from chromosome instable
cancers showed less (41%) and more
(22%) allelic imbalances than primaries
LOH varied between primaries and
mets; Lung and liver mets differed in
MSI markers
Albanese et al. (2004)19
Barnetson et al. (2003)20
Losi et al. (2005)21
Weber et al. (2006)22
Gross-Goupil et al.
(2003)23
Lung mets have deletions in 3p, 8p,
12q, 17q, 21q
Gains at 5p
Lung mets showed more alterations
than liver mets
Meta analysis: Gain of 1q, 6, 11, 16,
17q, 19 in mets; loss of 1p, 5q, 9p, 10q,
14q, 15q in at least 15% of specimens
Knosel et al. (2005)24
DPD levels lower in primary tumors
than LN mets
DPD, OPRT, UP and TP levels lower in
primary tumor than in mets
DPD and TP levels lower in primary
tumor than in mets
TS expression correlated between
primary tumor and met; no correlation
for DPD, TP, OPRT
Primary tumors overexpress E-cadherin
and Fas vs mets; decreased expression
of thymosin b-4, beta-catenin, MMP-7
VEGF levels equal in primary tumors
and liver mets
Overexpression of Gli1and Snail in
50% and 75% of metastases as
compared to primary tumors,
respectively
Vallbohmer et al. (2006)26
48% distant mets higher expression LN
= primary tumors
56% of primaries lost positivity in mets
29% of negative primaries had positive
mets
100% identical
6% of tumors and mets discordant
LN = primary tumors
14% of tumors and mets discordant
Dikicioglu et al. (2005)33
Diep CB et al. (2006)25
Inokuchi et al. (2004)27
Okumura et al. (2006)28
Kuramochi et al. (2006)29
Wang et al. (2004)30
Kuramochi et al. (2006)31
Feldmann et al. (2007)32
Krogerus and Leivonen
(2001)34
Tanner et al. (2001)35
Gancberg et al. (2002)15
Carlsson et al. (2004)36
Zidan et al. (2005)37
LN mets had fewer + tumor cells
Ding et al. (2001)38
Also less intense staining
Breast CXCR4
More intense staining on primary
Shim et al. (2006)39
tumors than in LN.
Breast Osteopontin
OPN levels higher in LN than primaries Allan et al. (2006)40
Breast Ki67, TS
Both proteins lower in LN mets
Calascibetta et al. (2006)41
Osteosarcoma
32% primaries+ P-glycoprotein;
Ferrari et al. (2004)42
68% mets53% primaries + Bcl-2;
84% mets
Lung
EGFR
33% of primaries and mets discordant
Italiano et al. (2006)17
Colorectal EGFR
6% of primaries and mets discordant
Italiano et al. (2005)43
Colorectal CD44
CD44s and CD44v6 staining
Bendardaf et al. (2006)44
significantly stronger in primary tumors
than mets
Colorectal MMP-9
100% of primary tumors MMP-9+ at
Illemann et al. (2006)45
invasive front versus 20% of mets
Colorectal E-cadherin
45% of primary tumors vs 81% of LN
Batistatou et al. (2006)46
mets
Colorectal E-cadherin
Primary tumor staining greater than
Elzagheid et al. (2006)47
mets
Head and neck S100A2
Primary tumor staining greater than LN Zhang et al. (2007)48
mets
Pancreatic EphA2
Primary tumor staining more frequent
Mudali et al. (2006)49
than in metastases to liver, lung, LN or
peritoneum.
Gastric Nm23, Kai1, Kiss1
Reduced expression in LN and liver
Guan-Zhen et al. (2007)50
mets
Abbreviations: CGH, comparative genomic hybridization; FISH, fluorescence in situ hybridization, LCM,
laser capture microdissection purification of tumor cells; LN, lymph node; mets, metastases; LOH, loss of
heterozygosity; MSI, microsattelite instability; SAGE, serial analysis of gene expression.
Breast
ER, PR
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