Abstract
Aim: To evaluate MGMTpromoter hypermethylation as prognostic factor in a retrospective study of 104 cases of glioblastoma multiforme (GBM). Materials and Methods: The O 6-methylguanine-DNA methyltransferase (MGMT) status was evaluated by methylation-specific PCR (MSP), immunohistochemistry and Western blotting analysis in formalin-fixed paraffin-embedded surgical samples. Results: The MGMT gene was found to be methylated in 29 of 101 tumors (28.7%) by MSP, according to the evaluation methods employed. By immunohistochemistry, different categories were identified on the basis of reaction intensity, percentage of positive cells and homogeneous or heterogeneous distribution. MSP did not correlate with immunohistochemistry, with the exception of the category with the highest percentage of positive cells and homogeneity of immunostaining. Western blotting analysis correlated with immunohistochemical findings (Pearson's correlation coefficient r=0268, p=0.0211), but not with MSP. By Kaplan-Meier survival analysis, radiotherapy was a significant prognostic factor (p=0.0001). When uncensored patients alone were considered, MGMT methylation status showed a significant correlation with survival (p=0.026). Temozolomide therapy correlated with survival (p=0.022), but not with MGMT methylation. After multivariate Cox regression analysis, only radiotherapy remained as an independent prognostic factor (p=0.0001). Conclusion: Correlation was inconclusive among MSP, immunohistochemistry and Western blotting analysis, despite the sophisticated score system for the immunohistochemical quantitative evaluation. MGMT expression is a complex event in which many factors beside epigenetic silencing are implicated.
| Original language | English |
|---|---|
| Pages (from-to) | 219-227 |
| Number of pages | 9 |
| Journal | Cancer Genomics and Proteomics |
| Volume | 6 |
| Issue number | 4 |
| Publication status | Published - Jul 2009 |
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Keywords
- Glioma
- MGMT
- Survival
- Temozolomide
ASJC Scopus subject areas
- Genetics
- Molecular Biology
- Cancer Research
- Biochemistry
Cite this
MGMT promoter hypermethylation in a series of 104 glioblastomas. / Mellai, Marta; Caldera, Valentina; Annovazzi, Laura; Chiò, Adriano; Lanotte, Michele; Cassoni, Paola; Finocchiaro, Gaetano; Schiffer, Davide.
In: Cancer Genomics and Proteomics, Vol. 6, No. 4, 07.2009, p. 219-227.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MGMT promoter hypermethylation in a series of 104 glioblastomas
AU - Mellai, Marta
AU - Caldera, Valentina
AU - Annovazzi, Laura
AU - Chiò, Adriano
AU - Lanotte, Michele
AU - Cassoni, Paola
AU - Finocchiaro, Gaetano
AU - Schiffer, Davide
PY - 2009/7
Y1 - 2009/7
N2 - Aim: To evaluate MGMTpromoter hypermethylation as prognostic factor in a retrospective study of 104 cases of glioblastoma multiforme (GBM). Materials and Methods: The O 6-methylguanine-DNA methyltransferase (MGMT) status was evaluated by methylation-specific PCR (MSP), immunohistochemistry and Western blotting analysis in formalin-fixed paraffin-embedded surgical samples. Results: The MGMT gene was found to be methylated in 29 of 101 tumors (28.7%) by MSP, according to the evaluation methods employed. By immunohistochemistry, different categories were identified on the basis of reaction intensity, percentage of positive cells and homogeneous or heterogeneous distribution. MSP did not correlate with immunohistochemistry, with the exception of the category with the highest percentage of positive cells and homogeneity of immunostaining. Western blotting analysis correlated with immunohistochemical findings (Pearson's correlation coefficient r=0268, p=0.0211), but not with MSP. By Kaplan-Meier survival analysis, radiotherapy was a significant prognostic factor (p=0.0001). When uncensored patients alone were considered, MGMT methylation status showed a significant correlation with survival (p=0.026). Temozolomide therapy correlated with survival (p=0.022), but not with MGMT methylation. After multivariate Cox regression analysis, only radiotherapy remained as an independent prognostic factor (p=0.0001). Conclusion: Correlation was inconclusive among MSP, immunohistochemistry and Western blotting analysis, despite the sophisticated score system for the immunohistochemical quantitative evaluation. MGMT expression is a complex event in which many factors beside epigenetic silencing are implicated.
AB - Aim: To evaluate MGMTpromoter hypermethylation as prognostic factor in a retrospective study of 104 cases of glioblastoma multiforme (GBM). Materials and Methods: The O 6-methylguanine-DNA methyltransferase (MGMT) status was evaluated by methylation-specific PCR (MSP), immunohistochemistry and Western blotting analysis in formalin-fixed paraffin-embedded surgical samples. Results: The MGMT gene was found to be methylated in 29 of 101 tumors (28.7%) by MSP, according to the evaluation methods employed. By immunohistochemistry, different categories were identified on the basis of reaction intensity, percentage of positive cells and homogeneous or heterogeneous distribution. MSP did not correlate with immunohistochemistry, with the exception of the category with the highest percentage of positive cells and homogeneity of immunostaining. Western blotting analysis correlated with immunohistochemical findings (Pearson's correlation coefficient r=0268, p=0.0211), but not with MSP. By Kaplan-Meier survival analysis, radiotherapy was a significant prognostic factor (p=0.0001). When uncensored patients alone were considered, MGMT methylation status showed a significant correlation with survival (p=0.026). Temozolomide therapy correlated with survival (p=0.022), but not with MGMT methylation. After multivariate Cox regression analysis, only radiotherapy remained as an independent prognostic factor (p=0.0001). Conclusion: Correlation was inconclusive among MSP, immunohistochemistry and Western blotting analysis, despite the sophisticated score system for the immunohistochemical quantitative evaluation. MGMT expression is a complex event in which many factors beside epigenetic silencing are implicated.
KW - Glioma
KW - MGMT
KW - Survival
KW - Temozolomide
UR - http://www.scopus.com/inward/record.url?scp=69549111318&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=69549111318&partnerID=8YFLogxK
M3 - Article
C2 - 19656999
AN - SCOPUS:69549111318
VL - 6
SP - 219
EP - 227
JO - Cancer Genomics and Proteomics
JF - Cancer Genomics and Proteomics
SN - 1109-6535
IS - 4
ER -