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Clinical Significance Of MGMT Expression In Human Glioma

Posted on:2016-10-02Degree:MasterType:Thesis
Country:ChinaCandidate:Z LiFull Text:PDF
GTID:2284330461969887Subject:Surgery
Abstract/Summary:PDF Full Text Request
O6-methylguanine-DNA methyltransferase(MGMT)was a kind of DNA repair proteins, widely existing in prokaryotes and human cells. MGMT gene located on chromosome encoding 10q26, was about 170 kh, including a total of five exons and four introns. After the administration of alkylating anticancer drugs, one or more reactive alkyl groups will be transferred to the guanine based of DNA molecules of tumor cells. Then the O6-guanine methylated to the form of O6-MG, the existence of O6-MG impeded the DNA replication process of the tumor cells, or affecting the gene expression, or resulting in the breakage of a DNA molecule, and ultimately reached the purposes of killing tumor cells. DNA repair protein MGMT can transfer the methylation from the O6-MG to the 145 cysteine residue of itself, being the new methylene acceptor, making the DNA chain of guanine tumor cells restored to O6-guanine. And the tumor cells were able to reproduction again. The existence of MGMT was considered to be the main reason that tumor cells was drug resistance to alkylating antineoplastic. Therefore, the study of MGMT in human glioma cells had its value.Objective:In the study, to explore the relationship between glioma and the activety of MGMT, we used the immunohistochemistry technique(IHC)for the hemmatoxylinand eosinstain(HE) of human glioma tissue. The results of the experiment expectually provide rational and effectual conduct in the clinical personalized themotherapy.Method:76 cases of glioma resection specimens were collected from Luzhou Medical College neurosurgery during January 2014-2014 December, and all of them were diagnosed by the department of Pathology. The pathological type were:35cases of astrocytoma, 9 cases of gum sarcoma, 21 cases of glioblastoma multiforme tumors, 6 cases of ependymorma and 5 cases of medulloblastoma. According to the WHO classification of tumors of the central nervous system standard grading( Ⅰ~ Ⅳ), 76 patients with glioma were divided into four groups, of which a total of 29 cases of grade Ⅰ, 15 cases of grade Ⅱ, 19 cases of grade Ⅲ, 13 cases of gradeⅣ. The grade ~ classified as benign, Ⅰ Ⅱ Ⅲ~ Ⅳgrade classified as malignant group, which organized a total of 44 cases of benign glioma, a total of 32 cases of malignant gliomas. The 76 patients were aged from 21 to 69 years, mean age(40.12 ± 5.74) years old, male 33 cases, female 43 cases. Normal brain tissue and cancerous tissue were taken as the control group, 10 cases in each one.Sequentially detected 76 cases of glioma tissues of different levels, 10 cases of adjacent normal tissues and 10 cases of carcinoma, according the MGMT expression to compare different levels of MGMT in glioma. Comparing the MGMT positive rate in different age, gender, and different types of pathology and observing its correlation. All data were compared using statistical methods.Results:1. In the 76 cases of glioma patients, MGMT expression for a total of 35 cases positive, and the total positive rate was 46.05%(35/76). 10 cases of patients with normal brain tissue, MGMT expression was positive in total 0 cases, the total positive rate of 0%(0/10). 10 cases of carcinoma adjacent, MGMT expression was positive in one case total, and is weakly positive, the total positive rate was 10%(1/10). The positive rate of MGMT in carcinoma adjacent tissue, normal tissue and the cancer tissue had a significant statistical significance(χ2 = 77.10, P = 0.000), and the differences in the cancer tissue was obviously significant(χ2=59.74, P=0.000; χ2=32.14, P=0.000). The positive rate of MGMT in normal tissues and adjacent tissues were not significantly different. In the four different classifications, the positive rate of grade Ⅰwas 48.28%; the positive rate of grade Ⅱwas 40.00%; the positive rate of grade Ⅲwas 42.11%; grade Ⅳwas 53.85%. MGMT-positive rate between different levels in glioma patients had no significant statistical significances(χ2=4.95,P>0.05). MGMT expression level of intensity had no significant statistical with glioma pathology unrelated(P> 0.05). The positive rate of MGMT in benign glioma was 45.45%(20/44); in malignant glioma was 46.87%(15/32). There were no significant statistical significances( χ2=0.78, P > 0.05).2. Male patients with MGMT positive rate was 42.42%(14/33); female patients with MGMT positive rate was 48.84%(21/43). MGMT positive rate in the comparison of different genders had no statistically significant difference(χ2 = 0.99, P> 0.05). Age spaning from 21 to 69 years, with an age of 10 years, were divided into five groups, the positive rates in different groups were: age 21 ~ 30, 44.44%( 4/9); age31 ~ 40, 46.43%( 13/28); age 41 ~ 50, 52.38%( 11/21); age 51 ~ 60, 40.00%(4/10);age 61~69, 37.50%(3/8). MGMT positive rate in the comparison of different ages had no statistically significant difference(χ2 =5.07, P> 0.05). MGMT positive rate in different pathological types were: 45.71% of astrocytoma(16/35), 55.56% of gum sarcoma(5/9), 42.86% of glioblastoma multiforme tumors(9/21), 50.00% of ependymorma(2/5) and 40.00% of medulloblastoma(3/6). MGMT positive rate in the comparison of different pathological types had no statistically significant difference(χ2 =6.26, P> 0.05).Conclusions : 1. MGMT of glioma tissues had significant differences in adjacent tissue, normal tissue and cancer tissue. 2. MGMT of glioma in different levels of development, had no significant differences. 3. MGMT expression was no significant differences in gender, age and tumor type. 4. The expression of MGMT protein to carry out clinical oncology has an extremely important role, MGMT could be used as glioma prognosis of patients may experience an important symbol of its alkylating anticancer drugs is one of resistance, for MGMT expression-positive patients, the choice of implementing individualized treatment plan, should avoid using alkylating anticancer drugs, thereby reducing the resistance of tumor cells to improve the prognosis of patients, improve the quality of life of patients. 5. With the development of modern medicine and molecular biology techniques, we also strive to find new MGMT organization, easier, faster detection means, to lay the foundation for further clinical application, as more patients and their families to relieve pain, reduce the burden.
Keywords/Search Tags:MGMT, glioma cancer, immunohistochemistry technique, pathology, expression
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