TY - JOUR
T1 - Gene methylation in pleural mesothelioma
T2 - Correlations with clinico-pathological features and patient's follow-up
AU - Destro, Annarita
AU - Ceresoli, Giovanni L.
AU - Baryshnikova, Ekaterina
AU - Garassino, Isabella
AU - Zucali, Paolo A.
AU - De Vincenzo, Fabio
AU - Bianchi, Paolo
AU - Morenghi, Emanuela
AU - Testori, Alberto
AU - Alloisio, Marco
AU - Santoro, Armando
AU - Roncalli, Massimo
PY - 2008/3
Y1 - 2008/3
N2 - Methylation of tumor suppressor genes is among the most frequent alterations in patients with malignant pleural mesothelioma (MPM). The aim of this study was to analyze the promoter methylation status of four tumor suppressor genes, p15INK4B, p16INK4A, RASSF1A and NORE1A in MPM. Samples of 79 MPM patients were analyzed using a methylation-specific PCR method. Associations between methylation status, clinico-pathological parameters (including proliferation index) and overall survival (OS) were examined. The analysis documented methylation in 30 cases (38%). The methylation frequency for individual genes was 19% for p15INK4B (n = 15), 11.4% for p16INK4A (n = 9), 20.2% for RASSF1A (n = 16) and 5.1% for Nore1A (n = 4). In the whole series methylation was associated to an increased proliferation index (P = 0.05). In patients treated with extrapleural pneumonectomy, methylated MPM showed a trend to a poorer OS in comparison to unmethylated cases (median OS 16 months vs. 35 months, P = 0.06, HR = 2.01, 95% CI 0.95-4.30). In the overall population, methylation did not correlate to patient outcome but a trend to an improved survival was detectable in ummethylated MPM treated with extrapleural pneumonectomy. This result suggests the need to select homogeneously treated and staged patients with MPM to address whether their methylation profile may impact on patient's survival.
AB - Methylation of tumor suppressor genes is among the most frequent alterations in patients with malignant pleural mesothelioma (MPM). The aim of this study was to analyze the promoter methylation status of four tumor suppressor genes, p15INK4B, p16INK4A, RASSF1A and NORE1A in MPM. Samples of 79 MPM patients were analyzed using a methylation-specific PCR method. Associations between methylation status, clinico-pathological parameters (including proliferation index) and overall survival (OS) were examined. The analysis documented methylation in 30 cases (38%). The methylation frequency for individual genes was 19% for p15INK4B (n = 15), 11.4% for p16INK4A (n = 9), 20.2% for RASSF1A (n = 16) and 5.1% for Nore1A (n = 4). In the whole series methylation was associated to an increased proliferation index (P = 0.05). In patients treated with extrapleural pneumonectomy, methylated MPM showed a trend to a poorer OS in comparison to unmethylated cases (median OS 16 months vs. 35 months, P = 0.06, HR = 2.01, 95% CI 0.95-4.30). In the overall population, methylation did not correlate to patient outcome but a trend to an improved survival was detectable in ummethylated MPM treated with extrapleural pneumonectomy. This result suggests the need to select homogeneously treated and staged patients with MPM to address whether their methylation profile may impact on patient's survival.
KW - Clinico-pathological parameters
KW - Extrapleural pneumonectomy
KW - Mesothelioma
KW - Methylation
KW - Proliferation
KW - Survival
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U2 - 10.1016/j.lungcan.2007.08.035
DO - 10.1016/j.lungcan.2007.08.035
M3 - Article
C2 - 17920725
AN - SCOPUS:40249088315
VL - 59
SP - 369
EP - 376
JO - Lung Cancer
JF - Lung Cancer
SN - 0169-5002
IS - 3
ER -