The prognostic impact of MGMT expression on low-grade gangliogliomas: a clinicopathological and immunohistochemical study
Ganglioglioma (GG) is an uncommon brain parenchymal neoplasm. Although most cases have indolent clinical behaviour, a subgroup of GGs does recur, especially in patients with unresectable disease. O6-methylguanine DNA methyltransferase (MGMT) is a DNA repair protein that removes mutagenic and cytotox...
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Veröffentlicht in: | Folia neuropathologica 2013, Vol.51 (4), p.275-282 |
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description | Ganglioglioma (GG) is an uncommon brain parenchymal neoplasm. Although most cases have indolent clinical behaviour, a subgroup of GGs does recur, especially in patients with unresectable disease. O6-methylguanine DNA methyltransferase (MGMT) is a DNA repair protein that removes mutagenic and cytotoxic adducts from O6-guanine in DNA. Lack of MGMT protein expression immunohistochemically is related to drug responses in patients with malignant glioma treated with alkylating agents. Furthermore, MGMT promoter methylation has also been investigated as an independent favourable prognostic factor for glioblastoma. The primary management is surgical resection for GGs and gross total resection is recommended. Despite infrequent use of chemotherapy for low-grade GGs, it was still introduced to a subset of patients, especially those who had unresectable disease. We assessed clinicopathological features of nine cases of low-grade GG to further elucidate the relationship between the status of the MGMT protein expression and the prognosis. This series included four men and five women with a mean age of 21.6 years at the first surgery. The mean postoperative follow-up period was 6 years. Only two patients had recurrent disease after 1.7 and 3.2 years of the first surgery. Immunohistochemically, 11.1% exhibited 3+ nuclear staining for MGMT protein, 11.1% exhibited 2+ staining, 33.3% exhibited 1+ staining, and 44.4% exhibited 0 staining. Tumours with more intensive MGMT protein expression (2+~3+ immunostaining) tended to recur more frequently (p < 0.05), corresponding to the worse prognostic predictive value of intensive MGMT staining. |
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Although most cases have indolent clinical behaviour, a subgroup of GGs does recur, especially in patients with unresectable disease. O6-methylguanine DNA methyltransferase (MGMT) is a DNA repair protein that removes mutagenic and cytotoxic adducts from O6-guanine in DNA. Lack of MGMT protein expression immunohistochemically is related to drug responses in patients with malignant glioma treated with alkylating agents. Furthermore, MGMT promoter methylation has also been investigated as an independent favourable prognostic factor for glioblastoma. The primary management is surgical resection for GGs and gross total resection is recommended. Despite infrequent use of chemotherapy for low-grade GGs, it was still introduced to a subset of patients, especially those who had unresectable disease. We assessed clinicopathological features of nine cases of low-grade GG to further elucidate the relationship between the status of the MGMT protein expression and the prognosis. This series included four men and five women with a mean age of 21.6 years at the first surgery. The mean postoperative follow-up period was 6 years. Only two patients had recurrent disease after 1.7 and 3.2 years of the first surgery. Immunohistochemically, 11.1% exhibited 3+ nuclear staining for MGMT protein, 11.1% exhibited 2+ staining, 33.3% exhibited 1+ staining, and 44.4% exhibited 0 staining. Tumours with more intensive MGMT protein expression (2+~3+ immunostaining) tended to recur more frequently (p < 0.05), corresponding to the worse prognostic predictive value of intensive MGMT staining.</description><identifier>ISSN: 1641-4640</identifier><identifier>EISSN: 1509-572X</identifier><identifier>DOI: 10.5114/fn.2013.39716</identifier><identifier>PMID: 24374955</identifier><language>eng</language><publisher>Poland</publisher><subject>Adult ; Biomarkers, Tumor - biosynthesis ; Biomarkers, Tumor - genetics ; Brain Neoplasms - diagnosis ; Brain Neoplasms - genetics ; Brain Neoplasms - metabolism ; Child ; Child, Preschool ; DNA Modification Methylases - biosynthesis ; DNA Modification Methylases - genetics ; DNA Repair Enzymes - biosynthesis ; DNA Repair Enzymes - genetics ; Female ; Follow-Up Studies ; Ganglioglioma - diagnosis ; Ganglioglioma - genetics ; Ganglioglioma - metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Neoplasm Grading ; Neoplasm Recurrence, Local - diagnosis ; Neoplasm Recurrence, Local - genetics ; Neoplasm Recurrence, Local - metabolism ; Prognosis ; Retrospective Studies ; Tumor Suppressor Proteins - biosynthesis ; Tumor Suppressor Proteins - genetics ; Young Adult</subject><ispartof>Folia neuropathologica, 2013, Vol.51 (4), p.275-282</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c398t-83ab5169f3513fc9fa581385a21150e06676997c67e92ec9ade4686e935c8f8e3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,860,4010,27900,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24374955$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chang, I-Wei</creatorcontrib><creatorcontrib>Hsu, Chao-Tien</creatorcontrib><creatorcontrib>Lin, Jui-Wei</creatorcontrib><creatorcontrib>Hung, Chih-Hsin</creatorcontrib><title>The prognostic impact of MGMT expression on low-grade gangliogliomas: a clinicopathological and immunohistochemical study</title><title>Folia neuropathologica</title><addtitle>Folia Neuropathol</addtitle><description>Ganglioglioma (GG) is an uncommon brain parenchymal neoplasm. Although most cases have indolent clinical behaviour, a subgroup of GGs does recur, especially in patients with unresectable disease. O6-methylguanine DNA methyltransferase (MGMT) is a DNA repair protein that removes mutagenic and cytotoxic adducts from O6-guanine in DNA. Lack of MGMT protein expression immunohistochemically is related to drug responses in patients with malignant glioma treated with alkylating agents. Furthermore, MGMT promoter methylation has also been investigated as an independent favourable prognostic factor for glioblastoma. The primary management is surgical resection for GGs and gross total resection is recommended. Despite infrequent use of chemotherapy for low-grade GGs, it was still introduced to a subset of patients, especially those who had unresectable disease. We assessed clinicopathological features of nine cases of low-grade GG to further elucidate the relationship between the status of the MGMT protein expression and the prognosis. This series included four men and five women with a mean age of 21.6 years at the first surgery. The mean postoperative follow-up period was 6 years. Only two patients had recurrent disease after 1.7 and 3.2 years of the first surgery. Immunohistochemically, 11.1% exhibited 3+ nuclear staining for MGMT protein, 11.1% exhibited 2+ staining, 33.3% exhibited 1+ staining, and 44.4% exhibited 0 staining. Tumours with more intensive MGMT protein expression (2+~3+ immunostaining) tended to recur more frequently (p < 0.05), corresponding to the worse prognostic predictive value of intensive MGMT staining.</description><subject>Adult</subject><subject>Biomarkers, Tumor - biosynthesis</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Brain Neoplasms - diagnosis</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain Neoplasms - metabolism</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>DNA Modification Methylases - biosynthesis</subject><subject>DNA Modification Methylases - genetics</subject><subject>DNA Repair Enzymes - biosynthesis</subject><subject>DNA Repair Enzymes - genetics</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Ganglioglioma - diagnosis</subject><subject>Ganglioglioma - genetics</subject><subject>Ganglioglioma - metabolism</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Male</subject><subject>Neoplasm Grading</subject><subject>Neoplasm Recurrence, Local - diagnosis</subject><subject>Neoplasm Recurrence, Local - genetics</subject><subject>Neoplasm Recurrence, Local - metabolism</subject><subject>Prognosis</subject><subject>Retrospective Studies</subject><subject>Tumor Suppressor Proteins - biosynthesis</subject><subject>Tumor Suppressor Proteins - genetics</subject><subject>Young Adult</subject><issn>1641-4640</issn><issn>1509-572X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kM1LxDAQxYMo7rp69Co5eumaNB9tvInoKuziZQVvJZsmbSRNatOi-9_b_VCYYYbh8Zj3A-AaoznDmN4ZP08RJnMiMsxPwBQzJBKWpR-n484pTiinaAIuYvxEiDIq0nMwSSnJqGBsCrbrWsO2C5UPsbcK2qaVqofBwNVitYb6p-10jDZ4OJYL30nVyVLDSvrK2bDrRsZ7KKFy1lsVWtnXwYXKKumg9OVo2Aw-1Db2QdW62d9jP5TbS3BmpIv66jhn4P35af34kizfFq-PD8tEEZH3SU7khmEuDGGYGCWMZDkmOZMpHqNqxHnGhcgUz7RItRLjd5TnXAvCVG5yTWbg9uA7pvwadOyLxkalnZNehyEWmHGeU4FHJjOQHKSqCzF22hRtZxvZbQuMih3twvhiR7vY0x71N0frYdPo8l_9h5f8Av3vfIc</recordid><startdate>2013</startdate><enddate>2013</enddate><creator>Chang, I-Wei</creator><creator>Hsu, Chao-Tien</creator><creator>Lin, Jui-Wei</creator><creator>Hung, Chih-Hsin</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope></search><sort><creationdate>2013</creationdate><title>The prognostic impact of MGMT expression on low-grade gangliogliomas: a clinicopathological and immunohistochemical study</title><author>Chang, I-Wei ; Hsu, Chao-Tien ; Lin, Jui-Wei ; Hung, Chih-Hsin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c398t-83ab5169f3513fc9fa581385a21150e06676997c67e92ec9ade4686e935c8f8e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Biomarkers, Tumor - biosynthesis</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Brain Neoplasms - diagnosis</topic><topic>Brain Neoplasms - genetics</topic><topic>Brain Neoplasms - metabolism</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>DNA Modification Methylases - biosynthesis</topic><topic>DNA Modification Methylases - genetics</topic><topic>DNA Repair Enzymes - biosynthesis</topic><topic>DNA Repair Enzymes - genetics</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Ganglioglioma - diagnosis</topic><topic>Ganglioglioma - genetics</topic><topic>Ganglioglioma - metabolism</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Male</topic><topic>Neoplasm Grading</topic><topic>Neoplasm Recurrence, Local - diagnosis</topic><topic>Neoplasm Recurrence, Local - genetics</topic><topic>Neoplasm Recurrence, Local - metabolism</topic><topic>Prognosis</topic><topic>Retrospective Studies</topic><topic>Tumor Suppressor Proteins - biosynthesis</topic><topic>Tumor Suppressor Proteins - genetics</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chang, I-Wei</creatorcontrib><creatorcontrib>Hsu, Chao-Tien</creatorcontrib><creatorcontrib>Lin, Jui-Wei</creatorcontrib><creatorcontrib>Hung, Chih-Hsin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><jtitle>Folia neuropathologica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chang, I-Wei</au><au>Hsu, Chao-Tien</au><au>Lin, Jui-Wei</au><au>Hung, Chih-Hsin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The prognostic impact of MGMT expression on low-grade gangliogliomas: a clinicopathological and immunohistochemical study</atitle><jtitle>Folia neuropathologica</jtitle><addtitle>Folia Neuropathol</addtitle><date>2013</date><risdate>2013</risdate><volume>51</volume><issue>4</issue><spage>275</spage><epage>282</epage><pages>275-282</pages><issn>1641-4640</issn><eissn>1509-572X</eissn><abstract>Ganglioglioma (GG) is an uncommon brain parenchymal neoplasm. Although most cases have indolent clinical behaviour, a subgroup of GGs does recur, especially in patients with unresectable disease. O6-methylguanine DNA methyltransferase (MGMT) is a DNA repair protein that removes mutagenic and cytotoxic adducts from O6-guanine in DNA. Lack of MGMT protein expression immunohistochemically is related to drug responses in patients with malignant glioma treated with alkylating agents. Furthermore, MGMT promoter methylation has also been investigated as an independent favourable prognostic factor for glioblastoma. The primary management is surgical resection for GGs and gross total resection is recommended. Despite infrequent use of chemotherapy for low-grade GGs, it was still introduced to a subset of patients, especially those who had unresectable disease. We assessed clinicopathological features of nine cases of low-grade GG to further elucidate the relationship between the status of the MGMT protein expression and the prognosis. This series included four men and five women with a mean age of 21.6 years at the first surgery. The mean postoperative follow-up period was 6 years. Only two patients had recurrent disease after 1.7 and 3.2 years of the first surgery. Immunohistochemically, 11.1% exhibited 3+ nuclear staining for MGMT protein, 11.1% exhibited 2+ staining, 33.3% exhibited 1+ staining, and 44.4% exhibited 0 staining. Tumours with more intensive MGMT protein expression (2+~3+ immunostaining) tended to recur more frequently (p < 0.05), corresponding to the worse prognostic predictive value of intensive MGMT staining.</abstract><cop>Poland</cop><pmid>24374955</pmid><doi>10.5114/fn.2013.39716</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adult Biomarkers, Tumor - biosynthesis Biomarkers, Tumor - genetics Brain Neoplasms - diagnosis Brain Neoplasms - genetics Brain Neoplasms - metabolism Child Child, Preschool DNA Modification Methylases - biosynthesis DNA Modification Methylases - genetics DNA Repair Enzymes - biosynthesis DNA Repair Enzymes - genetics Female Follow-Up Studies Ganglioglioma - diagnosis Ganglioglioma - genetics Ganglioglioma - metabolism Gene Expression Regulation, Neoplastic Humans Male Neoplasm Grading Neoplasm Recurrence, Local - diagnosis Neoplasm Recurrence, Local - genetics Neoplasm Recurrence, Local - metabolism Prognosis Retrospective Studies Tumor Suppressor Proteins - biosynthesis Tumor Suppressor Proteins - genetics Young Adult |
title | The prognostic impact of MGMT expression on low-grade gangliogliomas: a clinicopathological and immunohistochemical study |
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