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.

Stratification and Prognostic Relevance of Jass’s Molecular Classification of Colorectal Cancer

“…Therefore, although the frequency of CIMP-H in this study is lower than expected, it is in accordance with these larger European studies. More importantly, the poor prognostic effect observed here in patients with CIMP-H and CIMP-L tumors in comparison to those showing CIMP-negativity agrees with several works from other authors (Ward et al, 2003; Kim et al, 2009; Dahlin et al, 2010). In addition, our findings show no association of MGMT methylation with prognosis, a result which was also recently observed by Shima et al (2011).…”

Regulation of epigenetic traits of the glutathione S-transferase P1 gene: from detoxification toward cancer prevention and diagnosis

“…Moreover, GSTP1 hypermethylation and therefore gene silencing was associated to increased grades of mammary phyllodes tumors. As such GSTP1 methylation patterns allow distinguishing two groups: one benign unmethylated group as well as samples presenting hypermethylated GSTP1 gene promoters in the borderline/malignant tumor group (Kim et al, 2009). Recently, Miyake et al (2012) demonstrated that GSTP1 expression predicts poor pathological complete response to neoadjuvant chemotherapy in ER-negative breast cancer.…”

Recent insights into the molecular pathogenesis of mammary phyllodes tumours

“…Kim et al 41 studied hypermethylation via multiplex-nested PCR in 87 PTs and found a trend of increasing methylation with increasing grade, with a significant increase when borderline and malignant PTs were compared with benign PTs.…”