Additional table. Summary of genes reported to be methylated in ductal carcinoma in situ

Gene / Function of gene product / Percentage frequency of methylation (absolute numbers if reported) / Reference / Method used to assess methylation / Number of DCIS cases studied
NE / UDH / ADH / DCIS / IDC
14-3-3- / Cell cycle control / 0 (normal breast), 81.8 (9/11) adjacentto malignancy / 0 / 37.5 (3/8) / 83 / 96 (24/25) / Umbrichtet al. [35] (2001) / MSP / 6 P, 12 M
Present / Present / 66 / Lehmann et al. [36] (2002) / qMSP / 10 P, 27M
ABCB1 / Transmembrane transport protein / 0 / 40.7 (pure),44.1 (mixed) / 39.3 (11/28) / Muggerudet al. [47] (2010) / Pyrosequencing / 27 P, 34 M
10 (1/10) / 41.7 / 50 (7/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
APC1 / Wnt signaling pathway / 9 (3/32) / 39 (10/26) / 44 / 55 (34/62) / Hoqueet al. [46] (2009) / qMSP / 14 P, 33 M
7 (2/30) / 27 (8/30) / 34 / 38 (19/50) / Park et al. [49] (2011) / MethylLight / 35 P
0 / 69 (Korean), 83 (American) / Lee et al. [44] (2008) / QM-MSP / 52 P (American), 48 P (Korean)
10(1/10) / 41.7 / 50 (7/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
ATM / Cell cycle control / 0 / 13 / 12 (4/33) / Moelanset al. [48] (2011) / MS-MLPA / 33 M
BCAN / Lectican family of chondroitin sulfate proteoglycans / 70 / 89 (28/32) / Farynaet al. [54] (2012) / Methyl-CpGimmunoprecipitation with human CpG island arrays, validation with EpiTyperMassArray / 7 P, but results were combined with 6 LCIS cases.
BRCA1 / DNA repair / 0 / 25 (American), 33 (Korean) / Lee et al. [44] (2008) / QM-MSP / 52 P (American), 48 P (Korean)
0 / 23 / 21 (7/33) / Moelanset al. [48] (2011) / MS-MLPA / 33 M
BRCA2 / DNA repair / 0 / 10 / Lee et al. [44] (2008) / QM-MSP / 52 P (American), 48 P (Korean)
0 / 59 / 64 (21/33) / Moelanset al. [48] (2011) / MS-MLPA / 33 M
0 / 8.3 / 42.9 (6/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
CACNA1A / Voltage-dependent calcium channel / 10 (1/10) / 8.3 / 42.9 (6/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
CADM1 / Cell-cell adhesion / 0 / 8 / 18 (6/33) / Moelanset al. [48] (2011) / MS-MLPA / 33 M
10 (1/10) / 16.7 / 14.3 (2/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
CASP8 / Involved in apoptosis / 0 / 8.3 / 14.3 (2/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
CD44 / Cell-cell adhesion / 20 / 23 / 33 (11/33) / Moelanset al. [48] (2011) / MS-MLPA / 33 M
0 / 8.3 / 7.1 (1/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
20 (2/10) / 16.7 / 14.3 (2/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
CDH1 / Cell-cell adhesion / 12 (4/32) / 27 (7/26) / 30 / 42 (26/62) / Hoqueet al. [46] (2009) / qMSP / 36 M, 14 P
0 / 8 (American), 29 (Korean) / Lee et al. [44] (2008) / QM-MSP / 52 P (American), 48 P (Korean)
0 / 31.4 / LT 51.4 (19/ 37)
MT 43.8 (7/16) / Graff et al. [98] (2000) / MSP / 35
CDH13 / Promotes neovascularization, inhibits cell proliferation and invasiveness, increases susceptibility to apoptosis / 12 / 85 / 88 (29/33) / Moelanset al. [48] (2011) / MS-MLPA / 33 M
10 (1/10) / 25 / 28.6 (4/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
30 (3/10) / 66.7 / 71.4 (10/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
CDKN2A / Cell cycle control / 7.5 (3/40) / 35 (14/40) / 50 (LG), 68.2 (HG) / Liu et al. [43] (2008) / MethylLight / 18 LG, 22 HG
2.5 (1/40) / 32.5 (13/40) / 50 (LG), 63.6 (HG) / Liu et al. [43] (2008) / Methylation-sensitive restriction endonuclease-based method / 18 LG, 22 HG
0 (P), 5.9 (M) / 10.7 (3/28) / Muggerudet al. [47] (2010) / Pyrosequencing / 27 P, 34 M
0 / 0 / 3 / Present / Lehmann et al. [36] (2002) / qMSP / 30M, 10 P
0 / 3 / 0 / Moelanset al. [48] (2011) / MS-MLPA / 33 M
0 / 16.7 / 14.3 (2/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
CDKN2B / 10 (1/10) / 8.3 / 0 / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
CHFR / Cell cycle control / 0 / 3 / 0 / Moelanset al. [48] (2011) / MS-MLPA / 33 M
CTNNB1 / Wnt signaling pathway / 9 (3/32) / 15 (4/26) / 14 / 18 (11/62) / Hoqueet al. [46] (2009) / qMSP / 36M, 14 P
CCND2 / Cell cycle control / 0 / 32 / 52 (4/27) / Fackleret al. [37] (2003) / MSP / 44 P
0 / 56 (American), 60 (Korean) / Lee et al. [44] (2008) / QM-MSP. / 52 P (American), 48 P (Korean)
0 / 44 / 47 (8/17) / Evronet al. [33] (2001) / MSP / 13 M
0 / 0 / 60 / Present / Lehmann et al. [36] (2002) / q PCR / 30M, 10 P
56 / 71 / Puet al. [99] (2003) / MSP / 20
CCND2A / 0 / 75 / 78.6 (11/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
CCND2B / 10 (1/10) / 83.3 / 85.7 (12/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
DLEC1 / Tumor suppressor gene thought to inhibit cell proliferation, growth, and invasiveness / 7 (2/30) / 33 (10/30) / 37 / 40 (20/50) / Park et al. [49] (2011) / MethylLight / 35 P
ESR1 / Estrogen receptor, transcription factor / 25 (8/32) / 15 (4/26) / 24 / 24 (15/62) / Hoqueet al. [46] (2009) / qMSP / 36 M, 14 P
0 / 10 (American), 25 (Korean) / Lee et al. [44] (2008) / QM-MSP / 52 P (American), 48 P (Korean)
Present / 38 / 33 (11/33) / Moelanset al. [48] (2011) / MS-MLPA / 33 M
10 (1/10) / 25 / 28.6 (4/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
FHIT / Purine metabolism / 0 / 16.7 / 14.3 (2/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
FOXC1 / Transcription factor / 0 / 22 / 53.6 / Muggerudet al. [47] (2010) / Pyrosequencing / 27 P, 34 M
GATA5 / Transcription factor / 0 / 36 / 55 (18/33) / Moelanset al. [48] (2011) / MS-MLPA / 33
10 (1/10) / 25 / 35.7 (5/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
GFI1 / Transcription repressor / 83 / G1: 75 (9/12), G2: 88 (7/8) / Tommasiet al. [55] (2009) / Methylated-CpG island recovery assay-assisted microarray analysis, verified by COBRA / 6
GRIN2B / Neurotransmitter receptor / 0 / 3 (1/30) / 23 / 32 (16/50) / Park et al. [49] (2011) / MethylLight / 35 P
GSTP1 / Chemical detoxification enzyme / 0 / 16.7 (1/6) / 63 (includes LCIS) / 60 (9/15) / Pasqualiet al. [100] (2007) / Pyrosequencing / 12 M
0 / 44 / 45 (15/33) / Moelanset al. [48] (2011) / MS-MLPA / 33 M
0 / 3 (1/30) / 31 / 28 (14/50) / Park et al. [49] (2011) / MethylLight / 35 P
22.2 / 14.3 (4/28) / Muggerudet al. [47] (2010) / Pyrosequencing / 27 P, 34 M
9 (3/32) / 12 (3/26) / 16 / 23 (14/62) / Hoqueet al. [46] (2009) / qMSP / 36 M, 14 P
0 / 16.7 / 36.7 / 38.9 / Lee [56] (2007) / MSP / 49
0 / 33.3 / 35.7 (5/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
0 / 16.7 / 14.3 (2/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
H2AFXA / Histone H2A / 10 (1/10) / 16.7 / 7.1 (1/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
HIN1 / PI3K/AKT pathway / 61.5 / Kropet al. [52] (2001) / MSP / 13
0 / 67 (American), 73 (Korean) / Lee et al. [44] (2008) / QM-MSP / 52 P (American), 48 P (Korean)
68 / 60 (16/27) / Fackleret al. [37] (2003) / MSP / 44 P
3 (1/30) / 23 (7/30) / 34 / 36 (18/50) / Park et al. [49] (2011) / MethylLight / 35 P
10 (1/10) / 100 / 78.6 (11/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
0 / 50 / 64.3 (9/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
HOXA1 / Transcription factor / 13 (4/30) / 43 (13/30) / 80 / 76 (38/50) / Park et al. [49] (2011) / MethylLight / 35 P
HOXA10 / Transcription factor / 10 (3/30) / 3 (1/30) / 9 / 34 (17/50) / Park et al. [49] (2011) / MethylLight / 35 P
HOXB1B / Transcription factor / 50 / G1: 87 (13/15), G2: 89 (8/9), G3: 100 (8/8) / Tommasiet al. [55] (2009) / Methylated-CpG island recovery assay-assisted microarray analysis, verified by COBRA / 6
HOXD1 / Transcription factor / 67 / 72 (23/32) / Farynaet al. [54] (2012) / Methyl-CpGimmunoprecipitation with human CpG island arrays, validation with EpiTyperMassArray / 7 P, but results were combined with 6 LCIS cases.
HNF1B / Transcription factor / 50 / G1: 73 (11/15), G2: 56 (5/9), G3: 63 (5/8) / Tommasiet al. [55] (2009) / Methylated-CpG island recovery assay-assisted microarray analysis, verified by COBRA / 6
ID4A / DNA-binding protein inhibitor family / Present / 91.7 / 92.9 (13/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
ID4B / DNA-binding protein inhibitor family / 0 / 16.7 / 7.1 (1/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
IGF2 / Growth factor / 0 / 0 / 11 / 14 (7/50) / Park et al. [49] (2011) / MethylLight / 35 P
KCTD8 / Auxiliary subunit of GABA-B receptor / 77 / 97 (31/32) / Farynaet al. [54] (2012) / Methyl-CpGimmunoprecipitation with human CpG island arrays, validation with EpiTyperMassArray / 7 P, but results were combined with 6 LCIS cases.
KLF11 / Transcription factor / 62 / 91 (29/32) / Farynaet al. [54] (2012) / Methyl-CpGimmunoprecipitation with human CpG island arrays, validation with EpiTyperMassArray / 7 P, but results were combined with 6 LCIS cases.
MGMT / Dealkalates guanine in DNA / 3.7 / 3.6 (1/28) / Muggerudet al. [47] (2010) / Pyrosequencing. / 27 P, 34 M
7-8 / 15 / 42 (14/33) / Moelanset al. [48] (2011) / MS-MLPA / 33 M
MGMTA / Dealkalates guanine in DNA / 10 (1/10) / 16.7 / 57.1 (8/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
MGMTB / Dealkalates guanine in DNA / 10 (1/10) / 41.7 / 35.7 (5/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
MLH1 / DNA repair / 7.4 / 3.6 (1/28) / Muggerudet al. [47] (2010) / Pyrosequencing / 27 P, 34 M
MSH6 / DNA repair / 20 / 92 / 97 (32/33) / Moelanset al. [48] (2011) / MS-MLPA / 33 M
80 (8/10) / 75 / 85.7 (12/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
MT1G / Metallothionein, stores, transports, detoxifies heavy metals / 0 / 7 (2/30) / 14 / 32 (16/50) / Park et al. [49] (2011) / MethyLight / 35 P
NR2E1 / Nuclear receptor / 50 / G1: 53 (8/15) / Tommasiet al. [55] (2009) / Methylated-CpG island recovery assay-assisted microarray analysis, verified by COBRA / 6
NXPH1 / Member of neurexophilin family / 77 / 97 (31/32) / Farynaet al. [54] (2012) / Methyl-CpGimmunoprecipitation with human CpG island arrays, validation with EpiTyperMassArray / 7 P, but results were combined with 6 LCIS cases.
PAX5 / Transcription factor / 10 / 82 / 85 (28/33) / Moelanset al. [48] (2011) / MS-MLPA / 33 M
20 (2/10) / 58.3 / 28.6 (4/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
PAX6 / Transcription factor / 0 / 51 / 52 (17/33) / Moelanset al. [48] (2011) / MS-MLPA / 33 M
0 / 25 / 21.4 (3/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
PCDH10 / Cell-cell adhesion / 77 / 81 (26/32) / Farynaet al. [54] (2012) / Methyl-CpGimmunoprecipitation with human CpG island arrays, validation with EpiTyperMassArray / 7 P, but results were combined with 6 LCIS cases.
POU4F1 / Transcription factor / 69 / 94 (30/32) / Farynaet al. [54] (2012) / Methyl-CpGimmunoprecipitation with human CpG island arrays, validation with EpiTyperMassArray / 7 P, but results were combined with 6 LCIS cases.
PPP2R2B / Autophagy, oxidative stress-induced cell death / 0 / 55 / 78.6 (22/28) / Muggerudet al. [47] (2010) / Pyrosequencing / 27 P, 34 M
PTEN / PI3K/AKT signaling cascade / 0 / 18.5 / 14.3 (4/28) / Muggerudet al. [47] (2010) / Pyrosequencing / 27 P, 34 M
0 / 21 / 21 (7/33) / Moelanset al. [48] (2011) / MS-MLPA / 33 M
PYCARD / Apoptosis / 0 / 5 / 3 (1/33) / Moelanset al. [48] (2011) / MS-MLPA / 33 M
RARB / Retinoic acid pathway / 0 / 15 / 18 (6/33) / Moelanset al. [48] (2011) / MS-MLPA / 33 M
7 (2/30) / 7 (2/30) / 31 / 26 (13/50) / Park et al. [49] (2011) / MethyLight / 35 P
0 / 48 / 41 (11/27) / Fackleret al. [37] (2003) / MSP / 44 P
Present / 39 (American), 54 (Korean) / Lee et al. [44] (2008) / QM-MSP / 52 P (American),48 P (Korean)
60 / 64 / Puet al. [99] (2003) / MSP / 20
10 (1/10) / 16.7 / 7.1 (1/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
RASSF1A / Cell cycle control / 0 / 30 (P), 42 (M) / Present / Honorioet al. [38] (2003) / MSP / 10 P, 12 M
0 / 28.6 (2/7) / 50 (includes LCIS) / 66.7 (12/18) / Pasqualiet al. [100] (2007) / Pyrosequencing / 12 M cases and 4 LCIS-ILC cases
85.2 / 82.1 (23/28) / Muggerudet al. [47] (2010) / Pyrosequencing / 27 P, 34 M
40 (12/30) / 77 (23/30) / 89 / 76 (38/50) / Park et al. [49] (2011) / MethylLight / 35 P
Present / 75 (American), 85 (Korean) / Lee et al. [44] (2008) / QM-MSP / 52 P (American) , 48 P (Korean)
75 / 70 (19/27) / Fackleret al. [37] (2003) / MSP / 44 P
0 / Present / 83 / Present / Lehmann et al. [36] (2002) / qMSP / 10 P in total of 36
62 / 64 / Puet al. [99] (2003) / MSP / 20
100 / Alvarez et al. [101] (2012) / MSP / 5
0 / 83.3 / 71.4 (10/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
RASSF1B / Cell cycle control / 30 (3/10) / 91.7 / 71.4 (10/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
RB1 / Cell cycle control / 3-8 / 18 / 17 / Moelanset al. [48] (2011) / MS-MLPA / 33 M
RB1B / Cell cycle control / 10 (1/10) / 8.3 / 14.3 (2/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
RUNX3 / Transcription factor / 10 (1/10) / 76 (P), 74 (M) / 76 (16/21) / Subramaniamet al. [45] (2009) / MSP / 17 P, 23 M
0 / 0 / 17 / 24 (12/50) / Park et al. [49] (2011) / MethyLight / 35 P
20 (2/10) / 50 / 42.9 (6/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
RYR2 / Calcium ion channel / 46 / 66 (21/32) / Farynaet al. [54] (2012) / Methyl-CpGimmunoprecipitation with human CpG island arrays, validation with EpiTyperMassArray / 7,but results were combined with 6 LCIS cases.
SERPINB5 / Suppresses invasion, metastases, angiogenesis / 0 / 59 / Futscheret al. [41] (2004) / Bisulfite sequencing / 30 P
SFRP1 / Wnt signaling pathway / 0 / 17(G1), 69 (G2, G3) / 68 (19/28) / Lo et al. [42] (2006) / MSP, Bisulfite sequencing / 19
13 (4/30) / 3 (1/30) / 26 / 46 (23/50) / Park et al. [49] (2011) / MethyLight / 35 P
SFRP4 / Wnt signaling pathway / 0 / 7 (2/30) / 6 / 18 (9/50) / Park et al. [49] (2011) / MethyLight / 35 P
SFRP4A / 0 / 25 / 7.1 (1/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
SFRP4B / Wnt signaling pathway / 0 / 16.7 / 7.1 (1/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
SFRP5A / Wnt signaling pathway / 0 / 66.7 / 28.6 (4/14) / Verschuur-Maeset al. [53] (2012) / MS-MLPA / 6 P, 6 M
SIM1 / Transcription factor / 92 / 94 (30/32) / Farynaet al. [54] (2012) / Methyl-CpGimmunoprecipitation with human CpG island arrays, validation with EpiTyperMassArray / 7 P, but results were combined with 6 LCIS cases.
SLIT2 / Cellular migration / 50 / Alvarez et al. [101] (2012) / MSP / 4
STK11 / Cell polarity, metabolism, apoptosis / 7 / 36 / 27 (9/33) / Moelanset al. [48] (2011) / MS-MLPA / 33 M
TAC1 / Neurotransmitter / 46 / 66 (21/32) / Farynaet al. [54] (2012) / Methyl-CpGimmunoprecipitation with human CpG island arrays, validation with EpiTyperMassArray / 7,but results were combined with 6 LCIS cases.
TCF7L1 / Transcription factor / 69 / 84 (27/32) / Farynaet al. [54] (2012) / Methyl-CpGimmunoprecipitation with human CpG island arrays, validation with EpiTyperMassArray / 7,but results were combined with 6 LCIS cases.
TFAP2 / Transcription factor / 0 / 16 / 75 (120/161) / Douglas et al. [40] (2004) / MSP, Bisulfite sequencing / 19
THBS1 / Cell-cell interaction / 0 / 18 / 30 (10/33) / Moelanset al. [48] (2011) / MS-MLPA / 33 M
TIMP3 / Metalloproteinase inhibitor / 25 (8/32) / 42 (11/26) / 32 / 32 (20/62) / Hoqueet al. [46] (2009) / qMSP / 36 M, 14 P
TLX1 / Transcription factor / 67 / G1: 81 (13/16)
G2: 75 (6/8) / Tommasiet al. [55] (2009) / Methylated-CpG island recovery assay-assisted microarray analysis, verified by COBRA / 6
TMEFF2 / Transmembrane protein, may have role in PDGF signaling pathway / 40 (12/30) / 47 (14/30) / 86 / 76 (38/50) / Park et al. [49] (2011) / MethyLight / 35 P
TP53 / Cell cycle control / 0 / 21 / 15 (5/33) / Moelanset al. [48] (2011) / MS-MLPA / 33 M
0 (P), 33 (M) / 33 (3/9) / Kang et al. [34] (2001) / Bisulfite sequencing / 5 P, 6 M
TP73 / Cell cycle control / 9 / 23 / 21 (7/33) / Moelans et al. [48] (2011) / MS-MLPA / 33 M
10 (1/10) / 8.3 / 0 / Verschuur-Maes et al. [53] (2012) / MS-MLPA / 6 P, 6 M
TWIST1 / Transcription factor / 0 / 27 / 56 (15/27) / Fackler et al. [37] (2003) / MSP / 44 P
0 / 65 / Lee et al. [44] (2008) / QM-MSP / 52 P (American), 48P (Korean)
0 / 16.7 / 14.3 (2/14) / Verschuur-Maes et al. [53] (2012) / MS-MLPA / 6 P, 6 M
VHL / Regulation of angiogenesis / 0 / 10 / 15 (5/33) / Moelans et al. [48] (2011) / MS-MLPA / 33 M
WIF1 / Inhibits WNT proteins / 100 / Alvarez et al. [101] (2012) / MSP / 3
WT1 / Transcription factor / 11 / 85 / 70 (23/33) / Moelans et al. [48] (2011) / MS-MLPA / 33 M
20 (2/10) / 83.3 / 50 (7/14) / Verschuur-Maeset al. [53] 2012 / MS-MLPA / 6 P, 6 M

ADH, atypical ductal hyperplasia;COBRA, combined bisulfite restriction analysis; DCIS,ductal carcinoma in situ; G1,grade 1; G2,grade 2; G3,grade 3;HG, high-grade; IDC, invasive ductal carcinoma; LCIS, lobular carcinoma in situ;LG, low-grade; LT, locally invasive tumors; M, mixed ductal carcinoma in situ-invasive ductal carcinoma; MS-HRM,methylation-sensitive high-resolution melting; MS-MLPA,methylation-specific multiplex ligation-dependent probe amplification; MSP,methylation-specific polymerase chain reaction; MT, metastatic tumors; NE, normal epithelium; P, pure ductal carcinoma in situ;PDGF, platelet-derived growth factor; QM-MSP, quantitative multiplex-methylation-specific polymerase chain reaction;qMSP, quantitative methylation-specific polymerase chain reaction;UDH, usual ductal hyperplasia.