Supplementary Table 1: Selected Reports Comparing Primary Tumors and Metastases

Supplementary Table 1: Selected reports comparing primary tumors and metastases.

Method/Histology / Findings / Reference
Microarrays/SAGE
Lung / LCM
Nodal mets overall similar to primary tumors
Few distinct genes validated: IGFBP7, PAX5 / Hoang et al. (2005)1
Lung / Differential gene expression between brain mets and primary tumors / Kikuchiet al. (2006)2
Head and Neck / LN mets overall similar to primary tumors
MTA1 differentially expressed / Roepman et al. (2006)3
Esophageal / LCM
Multiple differentially expressed genes; Validation of SPP-1, CKS2, CCT5, STMN1, NDUFB9 overexpression and GJB2 underexpression in LN mets compared to primary tumors / Uchikado et al. (2006)4
Gastric / LCM
Decreased expression of OPCML, RNASE1, YES1 in LN met compared to primary tumor
Upregulation COX6C, SERPINB1, CCL22 in LN / Wanget al. (2006)5
Colorectal / LCM
Validated upregulation of MAP2,
N-WASP, NCAML1 in mets; S3RP downregulated / Yanagawaet al. (2001)6
Colorectal / Most primary tumors and mets co-clustered / Koehleret al. (2004)7
Colorectal / No significant differences / Takahashi Y et al. (2006)8
Breast / 79 differentially expressed genes between primary and LN; Validation of decreased expression of MMP2, FN, OSF2, COLXIA1 in LN mets / Hao X et al. (2004)9
Breast / Differential expression of IGFBP5, FN, MMP2, cyclin D1, enolase2 between primary tumor and LN met / Haoet al. (2004)9
Breast / Multiple differentially expressed genes detected betweenprimary and LN met / Zucchiet al.(2004)10
Breast / Primary tumors similar to mets / Weigelt et al. (2003)11
Breast / 70 gene prognostic signature in primary tumors and mets / Weigelt et al. (2005)12
Breast / Multiple genes differentially expressed between primary and LN met / Suzuki and Tarin13
Melanoma / LCM
47 genes up-regulated in metastases / Jaegeret al. (2007)14
FISH
Breast HER2 / 7% of primaries and mets discordant / Gancberget al. (2002)15
Breast HER2 / 3% of primaries and mets discordant / Gonget al. (2005)16
Lung EGFR / 27% of primaries and mets discordant / Italianoet al. (2006)17
Genetic alterations
Bladder / 4% tumors showed LOH in LN, not in primary 8% showed different patterns on LOH in distinct LN mets / Jones et al. (2005)18
Colorectal / 30% of primary tumors-mets discordant for Ki-ras mutation status; 7% discordant for p53. / Albanese et al. (2004)19
Colorectal / Distinct MSI at BAT25 locus and frequency of mutations in TCF4 in matched primaries and LNs of MSI cancers; equal frequencies at other loci. / Barnetson et al. (2003)20
Colorectal / Intratumoral genetic heterogeneity for p53 and K-ras lost in mets. / Losi et al. (2005)21
Colon CIN / Mets from chromosome instable cancers showed less (41%) and more (22%) allelic imbalances than primaries / Weber et al. (2006)22
Hepatocellular / LOH varied between primaries and mets; Lung and liver mets differed in MSI markers / Gross-Goupilet al. (2003)23
CGH
Colorectal / Lung mets have deletions in 3p, 8p, 12q, 17q, 21q
Gains at 5p
Lung mets showed more alterations than liver mets / Knoselet al. (2005)24
Colorectal / 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 / Diep CB et al. (2006)25
RNA expression levels
Colorectal / DPD levels lower in primary tumors than LN mets / Vallbohmer et al. (2006)26
Colorectal / DPD, OPRT, UP and TP levels lower in primary tumor than in mets / Inokuchi et al. (2004)27
Colorectal / DPD and TP levels lower in primary tumor than in mets / Okumuraet al. (2006)28
Colorectal / TS expression correlated between primary tumor and met; no correlation for DPD, TP, OPRT / Kuramochiet al. (2006)29
Colorectal / Primary tumors overexpress E-cadherin and Fas vs mets; decreased expression of thymosin b-4, beta-catenin, MMP-7 / Wang et al. (2004)30
Colorectal / VEGF levels equal in primary tumors and liver mets / Kuramochiet al. (2006)31
Pancreatic / Overexpression of Gli1and Snail in
50% and 75% of metastases as
compared to primary tumors,
respectively / Feldmannet al. (2007)32
Protein expression
Breast HER2 / 48% distant mets higher expression LN = primary tumors / Dikiciogluet al. (2005)33
Breast HER2 / 56% of primaries lost positivity in mets
29% of negative primaries had positive mets / Krogerus and Leivonen (2001)34
BreastHER2 / 100% identical / Tanneret al. (2001)35
BreastHER2 / 6% of tumors and mets discordant / Gancberget al. (2002)15
BreastHER2 / LN = primary tumors / Carlsson et al. (2004)36
BreastHER2 / 14% of tumors and mets discordant / Zidan et al. (2005)37
Breast ER, PR / LN mets had fewer + tumor cells
Also less intense staining / Ding et al. (2001)38
Breast CXCR4 / More intense staining on primary tumors than in LN. / Shim et al. (2006)39
BreastOsteopontin / OPN levels higher in LN than primaries / Allan et al. (2006)40
BreastKi67, TS / Both proteins lower in LN mets / Calascibettaet al. (2006)41
Osteosarcoma / 32% primaries+ P-glycoprotein;
68% mets53% primaries + Bcl-2;
84% mets / Ferrari et al. (2004)42
LungEGFR / 33% of primaries and mets discordant / Italianoet al. (2006)17
Colorectal EGFR / 6% of primaries and mets discordant / Italianoet al. (2005)43
Colorectal CD44 / CD44s and CD44v6 staining significantly stronger in primary tumors than mets / Bendardafet al. (2006)44
Colorectal MMP-9 / 100% of primary tumors MMP-9+ at invasive front versus 20% of mets / Illemannet al. (2006)45
Colorectal E-cadherin / 45% of primary tumors vs 81% of LN mets / Batistatouet al. (2006)46
Colorectal E-cadherin / Primary tumor staining greater than mets / Elzagheidet al. (2006)47
Head and neck S100A2 / Primary tumor staining greater than LN mets / Zhang et al. (2007)48
Pancreatic EphA2 / Primary tumor staining more frequent than in metastases to liver, lung, LN or peritoneum. / Mudaliet al. (2006)49
Gastric Nm23, Kai1, Kiss1 / Reduced expression in LN and liver mets / Guan-Zhenet al. (2007)50

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.

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