Concordance of Hypermethylated DNA and the Tumor Markers CA 15-3, CEA, and TPA in Serum during Monitoring of Patients with Advanced Breast Cancer.
The serological protein tumor markers CA 15-3, CEA, and TPA are frequently used to monitor tumor burden among metastatic breast cancer patients. Breast cancer is associated with global DNA hypomethylation and hypermethylation of some promoter regions. No monitoring study has yet investigated the interrelationship between protein tumor markers, the global DNA hypomethylation, and hypermethylated genes in serum from patients with advanced disease. Twenty-nine patients with histologically proven advanced breast cancer received first-line chemotherapy with epirubicin. Samples were collected prior to each treatment and prospectively analyzed for CA 15-3, CEA, and TPA. The same samples were retrospectively analyzed for the concentration of hypermethylated RASSF1A and for global DNA hypomethylation using LINE-1. Among patients with elevated concentrations of the protein markers, concordance could be observed between serial changes of the hypermethylated RASSF1A gene and the protein markers. Among patients with lower concentrations, RASSF1A could only be detected periodically. There was discordance between changes of the hypomethylated LINE-1 as compared to the protein markers. Circulating hypermethylated RASSF1A and protein markers may have similar kinetics during monitoring of tumor burden. Further investigations are needed to determine whether any of the hypermethylated DNA genes may provide predictive information during monitoring.
Department of Clinical Biochemistry, North Zealand Hospital, University of Copenhagen, Dyrehavevej 29, 3400 Hillerød, Denmark.
Søren
S
Kristiansen
Department of Clinical Biochemistry, North Zealand Hospital, University of Copenhagen, Dyrehavevej 29, 3400 Hillerød, Denmark.
Lars Mønster
LM
Jørgensen
Department of Clinical Biochemistry, North Zealand Hospital, University of Copenhagen, Dyrehavevej 29, 3400 Hillerød, Denmark.
Morten Høgh
MH
Hansen
Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, 2730 Herlev, Denmark.
Dorte
D
Nielsen
Department of Clinical Biochemistry, North Zealand Hospital, University of Copenhagen, Dyrehavevej 29, 3400 Hillerød, Denmark.
György
G
Sölétormos
D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002272:Carcinoembryonic Antigen / Q000097:blood*; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D019396:Tissue Polypeptide Antigen / Q000097:blood*; D025521:Tumor Suppressor Proteins / Q000235:genetics
D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D018396:Mucin-1; C411762:RASSF1 protein, human; D019396:Tissue Polypeptide Antigen; D025521:Tumor Suppressor Proteins