title: Borderline and malignant phyllodes tumors display similar promoter methylation profiles.
abstract: Mammary phyllodes tumors (PTs) are uncommon fibroepithelial neoplasms. On the basis of histologic criteria, PTs can be divided into benign, borderline, and malignant groups; however, the histologic distinction of PTs is often difficult and arbitrary. In breast cancer, promoter hypermethylation is a common phenomenon, but there are no data available concerning methylation status in PTs. The aim of this study was to assess whether the methylation profiles support the classification of PTs into three subgroups. A multiplex, nested, methylation-specific polymerase chain reaction approach was used to examine promoter methylation of five genes (GSTP1, HIN-1, RAR-beta, RASSF1A, and Twist) in 87 PTs (54 benign, 23 borderline, and 10 malignant). Immunohistochemical staining for GSTP1 was performed using tissue microarray blocks to determine whether GSTP1 promoter hypermethylation correlated with loss of GSTP1 expression. There was a trend of increasing methylation frequency with increasing grade of PTs. The methylation frequency of all genes and the mean number of methylated genes in borderline and malignant PTs were higher than those in benign PTs; however, there were no statistically significant differences between borderline and malignant PTs. GSTP1 promoter hypermethylation was associated with loss of GSTP1 expression (p < 0.001). These results suggest that PTs segregate into only two groups on the basis of their methylation profiles: the benign group and the combined borderline/malignant group.
authors.affiliation: Department of Pathology, Chonnam National University Medical School and Research Institute of Medical Sciences, Gwangju, South Korea.
authors.forename: Jo-Heon
authors.initials: JH
authors.lastname: Kim
authors.forename: Yoo Duk
authors.initials: YD
authors.lastname: Choi
authors.forename: Ji Shin
authors.initials: JS
authors.lastname: Lee
authors.forename: Jae Hyuk
authors.initials: JH
authors.lastname: Lee
authors.forename: Jong Hee
authors.initials: JH
authors.lastname: Nam
authors.forename: Chan
authors.initials: C
authors.lastname: Choi
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Park
authors.forename: Jung Han
authors.initials: JH
authors.lastname: Yoon
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D003557:Phyllodes Tumor / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines; D009687:Nuclear Proteins; C411762:RASSF1 protein, human; D018168:Receptors, Retinoic Acid; C434732:SCGB3A1 protein, human; C103173:TWIST1 protein, human; D025521:Tumor Suppressor Proteins; D051879:Twist-Related Protein 1; C082925:retinoic acid receptor beta; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi