Abstract

The aim of this article was to investigate the correlation between expression of O(6)-methylguanine-DNA methyltransferase (MGMT) in osteosarcoma and the curative effect of alkylating agent (Cis-diaminodichloroplatinum, CDDP). 42 male patients and 34 female patients with a median age of 17 years (9 to 43 years) were eligible for this study. According to histopathological types, there were 3 cases of telangiectatic osteogenic sarcoma, 22 cases of osteoblastic, 11 cases of chondroblastic and 16 cases of fibroblastic sarcoma. Immunohistochemical method was used to detect the expression of MGMT protein. The correlations between MGMT expression and the curative effect of CDDP on osteosarcoma have been investigated. It was shown by immunohistochemical staining that among 76 osteosarcoma biopsy specimens, 52 (68%) cases were positive, 27 (35%) cases were weak positive, 18 (24%), cases were moderate positive, and 7 (9%) cases were strong positive. There were no significant differences in MGMT expression among different pathological types of tumors (p>0.5). After CDDP chemotherapy, among pathologic specimens in which MGMT expression was positive, necrosis rates were as follows: grade I, 5 cases (38%); grade II, 7 cases (25%); grade III, 15 cases (21%); grade IV, 2 cases (23%). Osteosarcoma necrosis rate was low when the expression of MGMT protein was positive, whereas necrosis rate was high when there was a low level of MGMT expression (p<0.01). There was a significant negative correlation between the level of MGMT expression in osteosarcoma tissue and osteosarcoma necrosis rate after cisplatin chemotherapy.

Highlights

  • Chemotherapy plays a key role in the comprehensive treatment of osteosarcoma

  • The aim of this article was to investigate the correlation between expression of O -methylguanine-DNA methyltransferase (MGMT) in osteosarcoma and the curative effect of alkylating agent (Cis-diaminodichloroplatinum, CDDP). male patients and female patients with a median age of years were eligible for this study

  • There were no significant differences in MGMT expression among different pathological types of tumors (p> . )

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Summary

Introduction

Chemotherapy plays a key role in the comprehensive treatment of osteosarcoma. It has significantly increased the -year survival rate of osteosarcoma patients as well as the success rate of limb salvage surgeries. Results of intensive study on cell and molecular biology indicate that, to a large extent, the drug resistance of tumor cell are caused by two aspects. Gene MDRL encoding protein P-gp can actively transport the chemotherapeutic agents outside the cell, reducing the intracellular effective concentration, which makes the tumor cell escape the cytotoxicity of drugs. The strong repair function of tumor cell can significantly weaken the therapeutic effect of drugs. How to predict and conquer drug resistance of tumor cell is of great importance

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