Prognostic value of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression in glioblastoma excluding nontumour cells from the analysis

2017 ◽  
Vol 44 (2) ◽  
pp. 172-184 ◽  
Author(s):  
R. H. Dahlrot ◽  
J. Dowsett ◽  
S. Fosmark ◽  
A. Malmström ◽  
R. Henriksson ◽  
...  
Keyword(s):  
Protein Expression ◽  
Prognostic Value ◽  
Dna Methyltransferase ◽  
Methylguanine Dna Methyltransferase ◽  
Mgmt Protein

Predictive chemotherapy according to O6-methylguanine-DNA methyltransferase protein expression for treatment of malignant gliomas

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 12530-12530
Author(s):  
Z. Chen ◽  
J. Zhang ◽  
Q. Wu
Keyword(s):  
Protein Expression ◽  
Stable Disease ◽  
Dna Methyltransferase ◽  
Response Rate ◽  
Malignant Gliomas ◽  
Hematological Toxicity ◽  
Chemotherapeutic Regimen ◽  
Methylguanine Dna Methyltransferase ◽  
Mgmt Protein ◽  
Grade 3

12530 Background: To evaluate the response to predictable chemotherapy according to O6-methylguanine-DNA methyltransferase (MGMT) expression pattern and toxicity in patients with malignant gliomas. Methods: Twenty-eight patients with histologically confirmed malignant gliomas were enrolled in this study. The glioma tissues were examined for MGMT protein expression by immunohistochemistry. The chemotherapeutic regimen wasn’t consisted of nitrosourea or temozolomide in patients with MGMT positive expression, while no limitation using nitrosourea or temozolomide in patients with MGMT negative expression. The patients who received 2 or more than 2 cycles of chemotherapy were evaluated for response to therapy according WHO standard, and toxicity according National Cancer Institute (NCI) standard. Results: Twenty-four patients were used one regimen while 4 patients received two regimens chemotherapy, and thus overall 32 cases were evaluated for response to chemotherapy. The complete response (CR) was observed in 5 cases (16%),partial response (PR) in 6 cases (19%), stable disease (SD) was seen in 12 cases (38%), and 9 cases (28%) developed progressive disease (PD). Objective response rate (CR + PR) was 35%, and response plus stable disease rate (CR+PR+SD) was 73%. Hematological toxicity was the principal limiting side-effect observed in this study. Seven patients (25%, 7/28) experienced grade 3 or 4 leucopenia and one (4%,1/28) grade 4 thrombocytopenia who received platelet transfusion. No hemorrhagic event due to thrombocytopenia occurred. Non- hematological toxicity mainly was nausea/vomiting and alopecia. Grade 3 nausea/vomiting occurred in 7% of patients (2/28) and grade 3 alopecia in 7% of patients (2/28). Conclusions: The predictive chemotherapy according to MGMT protein expression in patients with malignant gliomas could improve overall response rate with acceptable side-effect, as compared with conventional chemotherapeutic regimen, and thus worth for further investigation. No significant financial relationships to disclose.

scholarly journals Prognostic value of TP53 expression and MGMT methylation in glioblastoma patients treated with temozolomide combined with other chemotherapies

2021 ◽  
Vol 152 (3) ◽  
pp. 541-549
Author(s):  
Maher Kurdi ◽  
Nadeem Shafique Butt ◽  
Saleh Baeesa ◽  
Badrah Alghamdi ◽  
Yazid Maghrabi ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Dna Methyltransferase ◽  
Chemotherapeutic Agents ◽  
Recurrence Interval ◽  
Mgmt Methylation ◽  
Conventional Radiotherapy ◽  
Methylguanine Dna Methyltransferase ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Temozolomide Chemotherapy

Abstract Objective To assess the recurrence interval and predictive significance of TP53 expression and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastomas treated with radiotherapy and combined chemotherapies, including temozolomide, lomustine, procarbazine and bevacizumab. Method We reviewed the clinical outcomes of 52 totally resected glioblastoma patients, who received conventional radiotherapy and temozolomide with other chemotherapeutic agents. Correlation of TP53 expression and MGMT promotor methylation with recurrence interval was analyzed using Kaplan Meier estimates. Results No significant association was found between MGMT promotor methylation and TP53 expression in glioblastomas (P-value = 0.158). Patients with non-methylated MGMT who received temozolomide chemotherapy with other chemotherapeutic agents showed significantly later recurrence (P-value = 0.007) compared with patients with non-methylated MGMT who received temozolomide alone. No significant difference was found in recurrence interval among glioblastoma patients with methylated MGMT who received temozolomide alone or with other chemotherapies (P-value = 0.667). Moreover, patients with non-TP53-expressing tumors who received temozolomide with other chemotherapies had significantly later recurrence (P-value = 0.04) compared with patients who received temozolomide alone. Conclusion Totally resected glioblastoma patients, with non-methylated MGMT or non-TP53-expressing tumors treated with radiotherapy and combined chemotherapies had a reduced chance of tumor recurrence and a more favorable outcome. Furthermore, both MGMT and TP53 are independent prognostic factors for glioblastoma.

Loss of O 6 -Methylguanine-DNA Methyltransferase Protein Expression Is a Favorable Prognostic Marker in Diffuse Large B-Cell Lymphoma

2006 ◽  
Vol 83 (4) ◽  
pp. 341-347 ◽  
Author(s):  
Toshihito Ohno ◽  
Junji Hiraga ◽  
Haruhiko Ohashi ◽  
Chiho Sugisaki ◽  
Eika Li ◽  
...  
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Prognostic Marker ◽  
Dna Methyltransferase ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Methylguanine Dna Methyltransferase ◽  
Large B Cell Lymphoma ◽  
Large B Cell

O6-Methylguanine-DNA methyltransferase expression and prognostic value in brain metastases of lung cancers

Lung Cancer ◽  
2010 ◽  
Vol 68 (3) ◽  
pp. 484-490 ◽  
Author(s):  
Pei-Fang Wu ◽  
Kuan-Ting Kuo ◽  
Lu-Ting Kuo ◽  
Yi-Ting Lin ◽  
Wei-Chung Lee ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Prognostic Value ◽  
Dna Methyltransferase ◽  
Lung Cancers ◽  
Methylguanine Dna Methyltransferase

scholarly journals Tim-3 protein expression with MGMT methylation status in glioblastoma and association with survival

2020 ◽  
Author(s):  
ji zhang ◽  
Xiaoli Wang ◽  
Shengquan Ye ◽  
Lijiao Liang ◽  
Yi Zhou ◽  
...  
Keyword(s):  
Protein Expression ◽  
Promoter Methylation ◽  
Immune Checkpoint ◽  
Dna Methyltransferase ◽  
Methylation Status ◽  
Prognostic Significance ◽  
Mgmt Promoter Methylation ◽  
Mgmt Methylation ◽  
Methylguanine Dna Methyltransferase ◽  
Mgmt Promoter

Abstract Background Understanding the molecular landscape of glioblastoma (GBM) is increasingly crucial for its therapy. Immune checkpoint molecules motivated the emergence of immune checkpoint-targeting therapeutic strategies. However, the prognostic significance of the immune checkpoint molecule T cell immunoglobulin mucin-3 (Tim-3) on tumor-infiltrating immune cells (TIICs) and O-6-Methylguanine-DNA methyltransferase (MGMT) methylation status remains to be fully elucidated. We aimed to develop an MGMT methylation status-associated immune prognostic signature for predicting prognosis in GBMs.Patients and Methods: A total of 84 patients with newly diagnosed GBM were involved. MGMT methylation status was retrospectively analyzed and the expression level of Tim-3 protein was investigated using immunohistochemistry (IHC). The correlation between Tim-3 protein expression and MGMT methylation status, and the prognosis was explored.Results The obtained data showed that Tim-3 protein was expressed at different levels in GBMs. Mesenchymal expression of Tim-3 protein in these tissues was 73.81% (62/84), including low 15.48% (13/84), moderate 7.14% (6/84) and strong expression 51.19% (43/84), respectively. Of the 48 patients whose tumors tested positive for MGMT methylation, the remaining 36 patients was negative.Conclusions We profiled the immune status in GBM with MGMT promoter methylation and established a local immune signature for GBM, which could independently identify patients with a favorable prognosis, indicating the relationship between prognosis and immune. MGMT promoter methylation with lower Tim-3 protein expression was statistically significantly associated with better survival.

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