PMID- 20696638
OWN - NLM
STAT- MEDLINE
DCOM- 20121211
LR  - 20211020
IS  - 2047-783X (Electronic)
IS  - 0949-2321 (Print)
IS  - 0949-2321 (Linking)
VI  - 15
IP  - 7
DP  - 2010
TI  - Methylated APC and GSTP1 genes in serum DNA correlate with the presence of 
      circulating blood tumor cells and are associated with a more aggressive and 
      advanced breast cancer disease.
PG  - 277-86
AB  - BACKGROUND: Tumor-related methylated DNA and circulating tumor cells (CTC) in the 
      peripheral blood might be of prognostic importance in breast cancer. Thus, the 
      aim of our study was to examine free methylated DNA and CTC in the blood from 
      breast cancer patients and to correlate it with clinicopathological features 
      known to influence prognosis. MATERIALS AND METHODS: We prospectively obtained 
      serum samples from 85 patients with breast cancer and 22 healthy volunteers. Sera 
      were analysed by methylation specific PCR (MethyLight PCR) for five genes: 
      adenomatous polyposis coli (APC), ras association domain family protein 1A 
      (RASSF1A), estrogen receptor 1 (ESR1), CDKN2A (p16) and glutathione s-transferase 
      pi 1 (GSTP1). Beta actin (ACTB) served as control. In parallel matched peripheral 
      blood of 63 patients was used to assay for circulating tumor cells in the 
      peripheral blood by a modified immunomagnetic AdnaTest BreastCancerSelect with 
      PCR detection for EPCAM, MUC1, MGB1 and SPDEF. RESULTS: A hypermethylation in the 
      APC gene in 29% (25/85), in RASSF1A in 26% (22/85), in GSTP1 in 18% (14/76) and 
      in ESR1 in 38% (32/85) of all breast cancer patients was detected. No 
      hypermethylation of CDKN2A was found (0/25). Blood samples of patients were 
      defined CTC positive by detecting the EPCAM 13% (8/63), MUC1 16% (10/63), MGB 9% 
      (5/55), SPDEF 12% (7/58) and in 27% detecting one or more genes (15/55). A 
      significant difference was seen in methylated APC DNA between cancer patients and 
      healthy volunteers. Moreover, methylated APC, RASSF1 and CTC were significantly 
      different in metastatic versus non-metastatic disease. In addition, the presence 
      of methylated APC, RASSF1A and CTC correlated significantly with AJCC-staging (p 
      = 0.001, p = 0.031 and 0.002, respectively). High incidences of methylations were 
      found for the genes RASSF1 and ESR1 in healthy individuals (both 23% 5/22). 
      Methylated GSTP1 was predominantly found in the serum of patients with large 
      primaries (p = 0.023) and was highly significantly correlated with positive 
      Her2/neu status (p = 0.003). Elevated serum CA15.3 was strongly correlated with 
      methylated APC and CTC detection (both p = 0.000). Methylated ESR1 failed to 
      exhibit significant correlations with any of the above mentioned parameters. The 
      presence of CTC in peripheral blood was significantly associated with methylated 
      APC (p = 0.012) and methylated GSTP1 (p = 0.001). CONCLUSION: The detection of 
      methylated APC and GSTP1 DNA in serum correlated with the presence of CTC in the 
      blood of breast cancer patients. Both methylated DNA and CTC correlated with a 
      more aggressive tumor biology and advanced disease.
FAU - Matuschek, C
AU  - Matuschek C
AD  - Department of Radiation Therapy and Radiation Oncology, University of Dusseldorf, 
      Germany.
FAU - Bolke, Edwin
AU  - Bolke E
FAU - Lammering, G
AU  - Lammering G
FAU - Gerber, P A
AU  - Gerber PA
FAU - Peiper, M
AU  - Peiper M
FAU - Budach, W
AU  - Budach W
FAU - Taskin, H
AU  - Taskin H
FAU - Prisack, H B
AU  - Prisack HB
FAU - Schieren, G
AU  - Schieren G
FAU - Orth, K
AU  - Orth K
FAU - Bojar, H
AU  - Bojar H
LA  - eng
PT  - Journal Article
PL  - England
TA  - Eur J Med Res
JT  - European journal of medical research
JID - 9517857
RN  - 0 (Biomarkers, Tumor)
RN  - 9007-49-2 (DNA)
RN  - EC 2.5.1.18 (GSTP1 protein, human)
RN  - EC 2.5.1.18 (Glutathione S-Transferase pi)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*genetics
MH  - Breast Neoplasms/blood/*diagnosis/genetics
MH  - DNA/blood
MH  - *DNA Methylation
MH  - Female
MH  - *Genes, APC
MH  - Genetic Loci
MH  - Glutathione S-Transferase pi/*genetics
MH  - Humans
MH  - Middle Aged
MH  - *Neoplastic Cells, Circulating
MH  - Prognosis
PMC - PMC3351951
EDAT- 2010/08/11 06:00
MHDA- 2012/12/12 06:00
PMCR- 2010/07/26
CRDT- 2010/08/11 06:00
PHST- 2010/08/11 06:00 [entrez]
PHST- 2010/08/11 06:00 [pubmed]
PHST- 2012/12/12 06:00 [medline]
PHST- 2010/07/26 00:00 [pmc-release]
AID - 2047-783X-15-7-277 [pii]
AID - 10.1186/2047-783x-15-7-277 [doi]
PST - ppublish
SO  - Eur J Med Res. 2010;15(7):277-86. doi: 10.1186/2047-783x-15-7-277.