TY - JOUR
T1 - Protein expression of a triad of frequently methylated genes, p73, p57 Kip2, and p15, has prognostic value in adult acute lymphocytic leukemia independently of its methylation status
AU - Bueso-Ramos, Carlos
AU - Xu, Yunling
AU - McDonnell, Timothy J.
AU - Brisbay, Shawn
AU - Pierce, Sherry
AU - Kantarjian, Hagop
AU - Rosner, Gary
AU - Garcia-Manero, Guillermo
PY - 2005
Y1 - 2005
N2 - Purpose: To study the relationship between protein expression and DNA methylation of a triad of cell-cycle regulatory genes known to be frequently methylated in adult acute lymphocytic leukemia (ALL). Patients and Methods: Protein expression of p73, p15, and p57Kip2 was analyzed by immunohistochemistry using a tissue microarray (TMA) platform. The TMA was constructed using pretreatment bone marrow biopsy specimens from 64 adult patients with ALL. Protein expression was then correlated with DNA methylation and relevant clinical biologic characteristics. Results: p73 protein expression was observed in 19 (30%) patients, cytoplasmic p15 in 19 (31%), and p57 in 40 (70%). Three patients (5%) had expression of all three proteins, 16 (29%) of two proteins, 31 (55%) of one protein, and six (11%) of zero proteins. An inverse association was observed between p73 DNA methylation and protein expression (P = .003). This effect was not observed for either p15 or p57Kip2. Expression of any of the proteins studied was not associated with any distinct biologic characteristic. By multivariate analysis, expression of p57 Kip2, cytoplasmic p15, or a combination of p57Kip2 with either p15 or p73 was associated with a better overall survival (P < .001, .04, and .03 respectively). Conclusion: Expression of a triad of cell cycle regulatory proteins that includes p73, p15, and p57Kip2 has prognostic value in adult patients with ALL independently of the methylation status of each gene.
AB - Purpose: To study the relationship between protein expression and DNA methylation of a triad of cell-cycle regulatory genes known to be frequently methylated in adult acute lymphocytic leukemia (ALL). Patients and Methods: Protein expression of p73, p15, and p57Kip2 was analyzed by immunohistochemistry using a tissue microarray (TMA) platform. The TMA was constructed using pretreatment bone marrow biopsy specimens from 64 adult patients with ALL. Protein expression was then correlated with DNA methylation and relevant clinical biologic characteristics. Results: p73 protein expression was observed in 19 (30%) patients, cytoplasmic p15 in 19 (31%), and p57 in 40 (70%). Three patients (5%) had expression of all three proteins, 16 (29%) of two proteins, 31 (55%) of one protein, and six (11%) of zero proteins. An inverse association was observed between p73 DNA methylation and protein expression (P = .003). This effect was not observed for either p15 or p57Kip2. Expression of any of the proteins studied was not associated with any distinct biologic characteristic. By multivariate analysis, expression of p57 Kip2, cytoplasmic p15, or a combination of p57Kip2 with either p15 or p73 was associated with a better overall survival (P < .001, .04, and .03 respectively). Conclusion: Expression of a triad of cell cycle regulatory proteins that includes p73, p15, and p57Kip2 has prognostic value in adult patients with ALL independently of the methylation status of each gene.
UR - http://www.scopus.com/inward/record.url?scp=21244483122&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=21244483122&partnerID=8YFLogxK
U2 - 10.1200/JCO.2005.02.998
DO - 10.1200/JCO.2005.02.998
M3 - Article
C2 - 15851765
AN - SCOPUS:21244483122
SN - 0732-183X
VL - 23
SP - 3932
EP - 3939
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 17
ER -