title: Detection of Slit2 promoter hypermethylation in tissue and serum samples from breast cancer patients.
abstract: Promoter hypermethylation has been shown to be a common mechanism for inactivation of tumor suppressor genes in breast cancer. The aim of this study was to investigate the prevalence of Slit2 promoter hypermethylation in both the tumor and serum samples of breast cancer patients with ductal carcinoma in situ (DCIS) or invasive breast carcinoma (IBC). The methylation status of Slit2 was investigated in 210 tissue samples (15 breast with no pathological findings, 26 DCIS, and 169 IBC samples) and 123 corresponding serum samples (15 breast with no pathological findings, 26 DCIS, and 82 IBC samples) using methylation-specific polymerase chain reaction. Immunohistochemical staining for Slit2 was also performed using tissue microarray blocks to determine whether Slit2 promoter hypermethylation correlated with loss of Slit2 expression. Slit2 promoter hypermethylation was not detected in breast tissue and serum samples from patients with no pathological findings. DCIS or IBC showed a statistically higher frequency of Slit2 promoter hypermethylation compared to breast with no pathological findings in both the tissue and serum samples; however, there were no statistically significant differences between DCIS and IBC samples. Similar Slit2 promoter hypermethylation patterns were seen in the tissue samples and corresponding serum specimens (p < 0.001). Slit2 promoter hypermethylation was associated with loss of Slit2 expression. These results suggest that Slit2 promoter hypermethylation appears to be responsible for functionally silencing Slit2 expression. Slit2 promoter hypermethylation may be considered as a possible serum marker for early detection of breast cancer.
authors: Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors: Ga-Eon
authors: GE
authors: Kim
authors: Kyung Hwa
authors: KH
authors: Lee
authors: Yoo Duk
authors: YD
authors: Choi
authors: Ji Shin
authors: JS
authors: Lee
authors: Jae Hyuk
authors: JH
authors: Lee
authors: Jong Hee
authors: JH
authors: Nam
authors: Chan
authors: C
authors: Choi
authors: Min Ho
authors: MH
authors: Park
authors: Jung Han
authors: JH
authors: Yoon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002278:Carcinoma in Situ / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D000098552:Slit Homolog 2 Protein
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D000098552:Slit Homolog 2 Protein