Borderline and malignant phyllodes tumors display similar promoter methylation profiles.
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.
Kim
Jo-Heon
JH
Department of Pathology, Chonnam National University Medical School and Research Institute of Medical Sciences, Gwangju, South Korea.
Choi
Yoo Duk
YD
Lee
Ji Shin
JS
Lee
Jae Hyuk
JH
Nam
Jong Hee
JH
Choi
Chan
C
Park
Min Ho
MH
Yoon
Jung Han
JH
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
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