Clinical significance of Stratifin, ERalpha and PR promoter methylation in tumor and serum DNA in Indian breast cancer patients.
OBJECTIVE
The objective of this study was to determine the concordance of promoter methylation of stratifin, ERalpha and PR in tumor and circulating DNA in breast cancer patients and their association with clinicopathological parameters and disease prognosis.


METHODS
Methylation specific PCR were carried out to investigate the promoter methylation status of stratifin, ERalpha and PR in tumor and circulating DNA in 100 breast cancer patients in a prospective study. The effect of promoter methylation on protein expression was evaluated by immunohistochemistry.


RESULTS
Significant association was observed between promoter methylation of stratifin in tumors (61%) and paired sera (56%) (r=0.78; p < or = 0.001). Loss of stratifin expression was observed in 47% tumors and was associated with poor overall survival (p=0.05). Significant correlation was observed between methylation status of ERalpha with PRB (p<0.0001, OR=20.8, 95% CI=7.4-58.0) and stratifin (p=0.003, OR=2.0, 95% CI=0.8-4.4).


CONCLUSIONS
This study underscores the potential utility of serum DNA methylation of these genes as surrogate for tumor DNA methylation as a promising tool for cancer diagnosis.
Mirza
Sameer
S
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
Sharma
Gayatri
G
Parshad
Rajinder
R
Srivastava
Anurag
A
Gupta
Siddartha Datta
SD
Ralhan
Ranju
R
D048948:14-3-3 Proteins; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000097:blood / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics*; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D005092:Exonucleases / Q000235:genetics* / Q000378:metabolism; D005095:Exoribonucleases; D005260:Female; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007194:India; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011980:Receptors, Progesterone / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis; D055815:Young Adult
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D009363:Neoplasm Proteins; D011980:Receptors, Progesterone; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human