TY - JOUR
T1 - Prognostic role of immunohistochemical analysis of 5 mc in myelodysplastic syndromes
AU - Poloni, Antonella
AU - Goteri, Gaia
AU - Zizzi, Antonio
AU - Serrani, Federica
AU - Trappolini, Silvia
AU - Costantini, Benedetta
AU - Mariani, Marianna
AU - Olivieri, Attilio
AU - Catarini, Massimo
AU - Centurioni, Riccardo
AU - Alesiani, Francesco
AU - Giantomassi, Federica
AU - Stramazzotti, Daniela
AU - Biagetti, Simona
AU - Alfonsi, Simona
AU - Berardinelli, Eleonora
AU - Leoni, Pietro
PY - 2013/9
Y1 - 2013/9
N2 - Background: Aberrant DNA methylation at CpG islands within promoters is increasingly recognised as a common event in human cancers and has been associated with the silencing of important tumour suppressor genes. Epigenetic therapy using hypomethylating agents has demonstrated clinical effectiveness; the drugs azacitidine and decitabine have been approved for the treatment of MDS. Method: We investigated the association between global DNA methylation and clinical outcome in MDS. We evaluated 134 MDS bone marrow trephine biopsies (BMTB) by immunohistochemistry and compared the results with those from an age-matched group of normal BMTB. Immunohistochemistry was performed on paraffin-embedded sections using the anti-5-methylcytosine (5mc) antibody. Results: Our results showed that the 5mc immunostaining score (M-score) of patients with MDS was higher than those of normal controls and that overall survival significantly correlated with global DNA methylation, age and IPSS score. Therefore, we found that patients with high levels of methylation had a shorter median overall survival (OS) compared with patients with lower levels. These immunohistochemistry results were confirmed by analysing global DNA methylation on LINE-1 sequences using the COBRA method and pyrosequencing. Conclusion: This study reports that global DNA methylation detected by immunohistochemistry predicts OS in MDS.
AB - Background: Aberrant DNA methylation at CpG islands within promoters is increasingly recognised as a common event in human cancers and has been associated with the silencing of important tumour suppressor genes. Epigenetic therapy using hypomethylating agents has demonstrated clinical effectiveness; the drugs azacitidine and decitabine have been approved for the treatment of MDS. Method: We investigated the association between global DNA methylation and clinical outcome in MDS. We evaluated 134 MDS bone marrow trephine biopsies (BMTB) by immunohistochemistry and compared the results with those from an age-matched group of normal BMTB. Immunohistochemistry was performed on paraffin-embedded sections using the anti-5-methylcytosine (5mc) antibody. Results: Our results showed that the 5mc immunostaining score (M-score) of patients with MDS was higher than those of normal controls and that overall survival significantly correlated with global DNA methylation, age and IPSS score. Therefore, we found that patients with high levels of methylation had a shorter median overall survival (OS) compared with patients with lower levels. These immunohistochemistry results were confirmed by analysing global DNA methylation on LINE-1 sequences using the COBRA method and pyrosequencing. Conclusion: This study reports that global DNA methylation detected by immunohistochemistry predicts OS in MDS.
KW - DNA methylation
KW - Hypomethylating agents
KW - Immunohistochemistry
KW - Myelodysplastic syndromes
KW - Pyrosequencing
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U2 - 10.1111/ejh.12145
DO - 10.1111/ejh.12145
M3 - Article
C2 - 23679560
AN - SCOPUS:84881663694
VL - 91
SP - 219
EP - 227
JO - European Journal of Haematology
JF - European Journal of Haematology
SN - 0902-4441
IS - 3
ER -