Mohamed Mokhtar1, Kazuya Kondo2, Toshiaki Namura3, Abdellah H K Ali4, Yui Fujita3, Chikako Takai3, Hiromitsu Takizawa5, Yasushi Nakagawa5, Hiroaki Toba5, Koichiro Kajiura5, Mitsuteru Yoshida5, Gyokei Kawakami5, Shoji Sakiyama5, Akira Tangoku5. 1. Department of Oncological Medical Services, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan; Department of Oncological Surgery, Minia Oncology Institute, Minia, Egypt. 2. Department of Oncological Medical Services, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan. Electronic address: kondo@clin.med.tokushima-u.ac.jp. 3. Department of Oncological Medical Services, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan. 4. Department of Respiratory Medicine, Sohag Faculty of Medicine, Sohag University, Sohag, Egypt. 5. Department of Thoracic, Endocrine and Oncological Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Abstract
OBJECTIVES: A key challenge in diagnosis and treatment of thymic epithelial tumors (TET) is in improving our understanding of the genetic and epigenetic changes of these relatively rare tumors. METHODS: Methylation specific PCR (MSP) and immunohistochemistry were applied to 66 TET to profile the methylation status of DNA repair gene O6-methylguanine DNA methyltransferase (MGMT) and its protein expression in TET to clarify the association between MGMT status and clinicopathological features, response to chemotherapy and overall survival. RESULTS: MGMT methylation was significantly more frequent in thymic carcinoma than in thymoma (17/23, 74% versus 13/44, 29%; P<0.001). Loss of expression of MGMT protein was significantly more frequent in thymic carcinoma than in thymoma (20/23, 87% versus 10/44, 23%; P<0.0001). There is a significant correlation between of MGMT methylation and loss of its protein expression (P<0.0003). MGMT methylation and loss of expression were significantly more frequent in advanced thymic epithelial tumors (III/IV) than in early tumors (I/II). CONCLUSION: MGMT methylation plays a soul role in development of TET, especially in thymic carcinoma. Therefore, translation of our results from basic molecular research to clinical practice may have important implication for considering MGMT methylation as a marker and a target of future therapies in TET.
OBJECTIVES: A key challenge in diagnosis and treatment of thymic epithelial tumors (TET) is in improving our understanding of the genetic and epigenetic changes of these relatively rare tumors. METHODS: Methylation specific PCR (MSP) and immunohistochemistry were applied to 66 TET to profile the methylation status of DNA repair gene O6-methylguanine DNA methyltransferase (MGMT) and its protein expression in TET to clarify the association between MGMT status and clinicopathological features, response to chemotherapy and overall survival. RESULTS:MGMT methylation was significantly more frequent in thymic carcinoma than in thymoma (17/23, 74% versus 13/44, 29%; P<0.001). Loss of expression of MGMT protein was significantly more frequent in thymic carcinoma than in thymoma (20/23, 87% versus 10/44, 23%; P<0.0001). There is a significant correlation between of MGMT methylation and loss of its protein expression (P<0.0003). MGMT methylation and loss of expression were significantly more frequent in advanced thymic epithelial tumors (III/IV) than in early tumors (I/II). CONCLUSION:MGMT methylation plays a soul role in development of TET, especially in thymic carcinoma. Therefore, translation of our results from basic molecular research to clinical practice may have important implication for considering MGMT methylation as a marker and a target of future therapies in TET.
Authors: Angela Lopomo; Roberta Ricciardi; Michelangelo Maestri; Anna De Rosa; Franca Melfi; Marco Lucchi; Alfredo Mussi; Fabio Coppedè; Lucia Migliore Journal: Int J Mol Sci Date: 2016-12-16 Impact factor: 5.923