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MGMT and MSH6 immunoexpression for functioning pituitary macroadenomas
Purpose Knowledge of biological behavior is crucial for clinical management of functioning pituitary macroadenomas. For recurrent cases unresponsive to standard treatment, temozolomide (TMZ) has been used as a therapeutic alternative. MGMT (O6-methyl-guanine-DNA methyltransferase) and MSH6 (mutS hom...
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| Published in: | Pituitary 2017-12, Vol.20 (6), p.643-653 |
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| Main Authors: | , , , , , , |
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| container_end_page | 653 |
| container_issue | 6 |
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| container_title | Pituitary |
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| creator | Micko, Alexander S. G. Wöhrer, Adelheid Höftberger, Romana Vila, Greisa Marosi, Christine Knosp, Engelbert Wolfsberger, Stefan |
| description | Purpose
Knowledge of biological behavior is crucial for clinical management of functioning pituitary macroadenomas. For recurrent cases unresponsive to standard treatment, temozolomide (TMZ) has been used as a therapeutic alternative. MGMT (O6-methyl-guanine-DNA methyltransferase) and MSH6 (mutS homolog 6) immunoexpression have been linked to the response to TMZ treatment and MGMT immunoexpression has been additionally linked to early recurrence of non-functioning pituitary adenomas. The aim of this study was to assess the prognostic value of MGMT and MSH6 immunoexpression for aggressive functioning pituitary adenomas.
Methods
The study cohort comprised a single center series of 76 patients who underwent an operation for functioning pituitary macroadenoma. We retrospectively compared 38 patients with postoperative persistent or recurrent disease with another set of 38 patients who were in endocrine remission.
Results
Low-to-moderate MGMT immunoexpression ( |
| doi_str_mv | 10.1007/s11102-017-0829-3 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_1938603204</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1954944233</sourcerecordid><originalsourceid>FETCH-LOGICAL-p212t-ae6d5cced57853f1e6c9a216aa0b61676468e947f5edbdac38aacb7e6b367d653</originalsourceid><addsrcrecordid>eNpdkU1LAzEQhoMotlZ_gBdZ8OIlmu_sHqVYFVo8WMFbyCbZsqWbrMku6L83pQriaWaYZ4Z55wXgEqNbjJC8SxhjRCDCEqKSVJAegSnmkkLJED3OOS0FpAy_T8BZSluE8hRlp2BCygqhEvEpWKweV-tCe1usXp9E0Xbd6IP77KNLqQ2-aEIsmtGbIRet3xR9O4ztoONX0WkTg7bOh06nc3DS6F1yFz9xBt4WD-v5E1y-PD7P75ewJ5gMUDthuTHOclly2mAnTKUJFlqjWmAhBROlq5hsuLO11YaWWptaOlFTIa3gdAZuDnv7GD5GlwbVtcm43U57F8akcJUlI0oQy-j1P3QbxujzdZnirGKMUJqpqx9qrDtnVR_bLqtTvx_KADkAKbf8xsU_a5Da26AONqhsg9rboCj9BnuHd8k</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1954944233</pqid></control><display><type>article</type><title>MGMT and MSH6 immunoexpression for functioning pituitary macroadenomas</title><source>Springer Nature</source><creator>Micko, Alexander S. G. ; Wöhrer, Adelheid ; Höftberger, Romana ; Vila, Greisa ; Marosi, Christine ; Knosp, Engelbert ; Wolfsberger, Stefan</creator><creatorcontrib>Micko, Alexander S. G. ; Wöhrer, Adelheid ; Höftberger, Romana ; Vila, Greisa ; Marosi, Christine ; Knosp, Engelbert ; Wolfsberger, Stefan</creatorcontrib><description>Purpose
Knowledge of biological behavior is crucial for clinical management of functioning pituitary macroadenomas. For recurrent cases unresponsive to standard treatment, temozolomide (TMZ) has been used as a therapeutic alternative. MGMT (O6-methyl-guanine-DNA methyltransferase) and MSH6 (mutS homolog 6) immunoexpression have been linked to the response to TMZ treatment and MGMT immunoexpression has been additionally linked to early recurrence of non-functioning pituitary adenomas. The aim of this study was to assess the prognostic value of MGMT and MSH6 immunoexpression for aggressive functioning pituitary adenomas.
Methods
The study cohort comprised a single center series of 76 patients who underwent an operation for functioning pituitary macroadenoma. We retrospectively compared 38 patients with postoperative persistent or recurrent disease with another set of 38 patients who were in endocrine remission.
Results
Low-to-moderate MGMT immunoexpression (<50%) was significantly more frequent in the group with persistent/recurrent disease than in cases of endocrine remission (66 vs. 21%, p < 0.001). Furthermore, adenomas with low-to-moderate MGMT immunoexpression were significantly more often recurrent (76 vs. 30%, p < 0.001) and invasive (64 vs. 28%, p = 0.002).
Conclusion
In our series, low-to-moderate MGMT immunoexpression was the only marker that significantly correlated with surgical invasiveness and recurrence in functioning pituitary macroadenomas. Therefore, in the future, MGMT status may be considered an additional marker for understanding the biological behavior of pituitary adenomas.</description><identifier>ISSN: 1386-341X</identifier><identifier>EISSN: 1573-7403</identifier><identifier>DOI: 10.1007/s11102-017-0829-3</identifier><identifier>PMID: 28900805</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adult ; Antineoplastic Agents, Alkylating - therapeutic use ; Dacarbazine - analogs & derivatives ; Dacarbazine - therapeutic use ; DNA methyltransferase ; DNA Modification Methylases - metabolism ; DNA Repair Enzymes - metabolism ; DNA-Binding Proteins - metabolism ; Endocrinology ; Female ; Guanine ; Human Physiology ; Humans ; Invasiveness ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; MSH6 protein ; Neoplasm Recurrence, Local - drug therapy ; Neoplasm Recurrence, Local - immunology ; Neoplasm Recurrence, Local - metabolism ; O-Methylguanine-DNA Methyltransferase - metabolism ; O6-methylguanine-DNA methyltransferase ; Pituitary ; Pituitary Neoplasms - drug therapy ; Pituitary Neoplasms - immunology ; Pituitary Neoplasms - metabolism ; Remission ; Retrospective Studies ; Temozolomide ; Tumor Suppressor Proteins - metabolism ; Tumors</subject><ispartof>Pituitary, 2017-12, Vol.20 (6), p.643-653</ispartof><rights>The Author(s) 2017</rights><rights>Pituitary is a copyright of Springer, 2017.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-p212t-ae6d5cced57853f1e6c9a216aa0b61676468e947f5edbdac38aacb7e6b367d653</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28900805$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Micko, Alexander S. G.</creatorcontrib><creatorcontrib>Wöhrer, Adelheid</creatorcontrib><creatorcontrib>Höftberger, Romana</creatorcontrib><creatorcontrib>Vila, Greisa</creatorcontrib><creatorcontrib>Marosi, Christine</creatorcontrib><creatorcontrib>Knosp, Engelbert</creatorcontrib><creatorcontrib>Wolfsberger, Stefan</creatorcontrib><title>MGMT and MSH6 immunoexpression for functioning pituitary macroadenomas</title><title>Pituitary</title><addtitle>Pituitary</addtitle><addtitle>Pituitary</addtitle><description>Purpose
Knowledge of biological behavior is crucial for clinical management of functioning pituitary macroadenomas. For recurrent cases unresponsive to standard treatment, temozolomide (TMZ) has been used as a therapeutic alternative. MGMT (O6-methyl-guanine-DNA methyltransferase) and MSH6 (mutS homolog 6) immunoexpression have been linked to the response to TMZ treatment and MGMT immunoexpression has been additionally linked to early recurrence of non-functioning pituitary adenomas. The aim of this study was to assess the prognostic value of MGMT and MSH6 immunoexpression for aggressive functioning pituitary adenomas.
Methods
The study cohort comprised a single center series of 76 patients who underwent an operation for functioning pituitary macroadenoma. We retrospectively compared 38 patients with postoperative persistent or recurrent disease with another set of 38 patients who were in endocrine remission.
Results
Low-to-moderate MGMT immunoexpression (<50%) was significantly more frequent in the group with persistent/recurrent disease than in cases of endocrine remission (66 vs. 21%, p < 0.001). Furthermore, adenomas with low-to-moderate MGMT immunoexpression were significantly more often recurrent (76 vs. 30%, p < 0.001) and invasive (64 vs. 28%, p = 0.002).
Conclusion
In our series, low-to-moderate MGMT immunoexpression was the only marker that significantly correlated with surgical invasiveness and recurrence in functioning pituitary macroadenomas. Therefore, in the future, MGMT status may be considered an additional marker for understanding the biological behavior of pituitary adenomas.</description><subject>Adult</subject><subject>Antineoplastic Agents, Alkylating - therapeutic use</subject><subject>Dacarbazine - analogs & derivatives</subject><subject>Dacarbazine - therapeutic use</subject><subject>DNA methyltransferase</subject><subject>DNA Modification Methylases - metabolism</subject><subject>DNA Repair Enzymes - metabolism</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Endocrinology</subject><subject>Female</subject><subject>Guanine</subject><subject>Human Physiology</subject><subject>Humans</subject><subject>Invasiveness</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>MSH6 protein</subject><subject>Neoplasm Recurrence, Local - drug therapy</subject><subject>Neoplasm Recurrence, Local - immunology</subject><subject>Neoplasm Recurrence, Local - metabolism</subject><subject>O-Methylguanine-DNA Methyltransferase - metabolism</subject><subject>O6-methylguanine-DNA methyltransferase</subject><subject>Pituitary</subject><subject>Pituitary Neoplasms - drug therapy</subject><subject>Pituitary Neoplasms - immunology</subject><subject>Pituitary Neoplasms - metabolism</subject><subject>Remission</subject><subject>Retrospective Studies</subject><subject>Temozolomide</subject><subject>Tumor Suppressor Proteins - metabolism</subject><subject>Tumors</subject><issn>1386-341X</issn><issn>1573-7403</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNpdkU1LAzEQhoMotlZ_gBdZ8OIlmu_sHqVYFVo8WMFbyCbZsqWbrMku6L83pQriaWaYZ4Z55wXgEqNbjJC8SxhjRCDCEqKSVJAegSnmkkLJED3OOS0FpAy_T8BZSluE8hRlp2BCygqhEvEpWKweV-tCe1usXp9E0Xbd6IP77KNLqQ2-aEIsmtGbIRet3xR9O4ztoONX0WkTg7bOh06nc3DS6F1yFz9xBt4WD-v5E1y-PD7P75ewJ5gMUDthuTHOclly2mAnTKUJFlqjWmAhBROlq5hsuLO11YaWWptaOlFTIa3gdAZuDnv7GD5GlwbVtcm43U57F8akcJUlI0oQy-j1P3QbxujzdZnirGKMUJqpqx9qrDtnVR_bLqtTvx_KADkAKbf8xsU_a5Da26AONqhsg9rboCj9BnuHd8k</recordid><startdate>20171201</startdate><enddate>20171201</enddate><creator>Micko, Alexander S. G.</creator><creator>Wöhrer, Adelheid</creator><creator>Höftberger, Romana</creator><creator>Vila, Greisa</creator><creator>Marosi, Christine</creator><creator>Knosp, Engelbert</creator><creator>Wolfsberger, Stefan</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20171201</creationdate><title>MGMT and MSH6 immunoexpression for functioning pituitary macroadenomas</title><author>Micko, Alexander S. G. ; Wöhrer, Adelheid ; Höftberger, Romana ; Vila, Greisa ; Marosi, Christine ; Knosp, Engelbert ; Wolfsberger, Stefan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p212t-ae6d5cced57853f1e6c9a216aa0b61676468e947f5edbdac38aacb7e6b367d653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Antineoplastic Agents, Alkylating - therapeutic use</topic><topic>Dacarbazine - analogs & derivatives</topic><topic>Dacarbazine - therapeutic use</topic><topic>DNA methyltransferase</topic><topic>DNA Modification Methylases - metabolism</topic><topic>DNA Repair Enzymes - metabolism</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Endocrinology</topic><topic>Female</topic><topic>Guanine</topic><topic>Human Physiology</topic><topic>Humans</topic><topic>Invasiveness</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>MSH6 protein</topic><topic>Neoplasm Recurrence, Local - drug therapy</topic><topic>Neoplasm Recurrence, Local - immunology</topic><topic>Neoplasm Recurrence, Local - metabolism</topic><topic>O-Methylguanine-DNA Methyltransferase - metabolism</topic><topic>O6-methylguanine-DNA methyltransferase</topic><topic>Pituitary</topic><topic>Pituitary Neoplasms - drug therapy</topic><topic>Pituitary Neoplasms - immunology</topic><topic>Pituitary Neoplasms - metabolism</topic><topic>Remission</topic><topic>Retrospective Studies</topic><topic>Temozolomide</topic><topic>Tumor Suppressor Proteins - metabolism</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Micko, Alexander S. G.</creatorcontrib><creatorcontrib>Wöhrer, Adelheid</creatorcontrib><creatorcontrib>Höftberger, Romana</creatorcontrib><creatorcontrib>Vila, Greisa</creatorcontrib><creatorcontrib>Marosi, Christine</creatorcontrib><creatorcontrib>Knosp, Engelbert</creatorcontrib><creatorcontrib>Wolfsberger, Stefan</creatorcontrib><collection>SpringerOpen</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Pituitary</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Micko, Alexander S. G.</au><au>Wöhrer, Adelheid</au><au>Höftberger, Romana</au><au>Vila, Greisa</au><au>Marosi, Christine</au><au>Knosp, Engelbert</au><au>Wolfsberger, Stefan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MGMT and MSH6 immunoexpression for functioning pituitary macroadenomas</atitle><jtitle>Pituitary</jtitle><stitle>Pituitary</stitle><addtitle>Pituitary</addtitle><date>2017-12-01</date><risdate>2017</risdate><volume>20</volume><issue>6</issue><spage>643</spage><epage>653</epage><pages>643-653</pages><issn>1386-341X</issn><eissn>1573-7403</eissn><abstract>Purpose
Knowledge of biological behavior is crucial for clinical management of functioning pituitary macroadenomas. For recurrent cases unresponsive to standard treatment, temozolomide (TMZ) has been used as a therapeutic alternative. MGMT (O6-methyl-guanine-DNA methyltransferase) and MSH6 (mutS homolog 6) immunoexpression have been linked to the response to TMZ treatment and MGMT immunoexpression has been additionally linked to early recurrence of non-functioning pituitary adenomas. The aim of this study was to assess the prognostic value of MGMT and MSH6 immunoexpression for aggressive functioning pituitary adenomas.
Methods
The study cohort comprised a single center series of 76 patients who underwent an operation for functioning pituitary macroadenoma. We retrospectively compared 38 patients with postoperative persistent or recurrent disease with another set of 38 patients who were in endocrine remission.
Results
Low-to-moderate MGMT immunoexpression (<50%) was significantly more frequent in the group with persistent/recurrent disease than in cases of endocrine remission (66 vs. 21%, p < 0.001). Furthermore, adenomas with low-to-moderate MGMT immunoexpression were significantly more often recurrent (76 vs. 30%, p < 0.001) and invasive (64 vs. 28%, p = 0.002).
Conclusion
In our series, low-to-moderate MGMT immunoexpression was the only marker that significantly correlated with surgical invasiveness and recurrence in functioning pituitary macroadenomas. Therefore, in the future, MGMT status may be considered an additional marker for understanding the biological behavior of pituitary adenomas.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>28900805</pmid><doi>10.1007/s11102-017-0829-3</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | Springer Nature |
| subjects | Adult Antineoplastic Agents, Alkylating - therapeutic use Dacarbazine - analogs & derivatives Dacarbazine - therapeutic use DNA methyltransferase DNA Modification Methylases - metabolism DNA Repair Enzymes - metabolism DNA-Binding Proteins - metabolism Endocrinology Female Guanine Human Physiology Humans Invasiveness Male Medicine Medicine & Public Health Middle Aged MSH6 protein Neoplasm Recurrence, Local - drug therapy Neoplasm Recurrence, Local - immunology Neoplasm Recurrence, Local - metabolism O-Methylguanine-DNA Methyltransferase - metabolism O6-methylguanine-DNA methyltransferase Pituitary Pituitary Neoplasms - drug therapy Pituitary Neoplasms - immunology Pituitary Neoplasms - metabolism Remission Retrospective Studies Temozolomide Tumor Suppressor Proteins - metabolism Tumors |
| title | MGMT and MSH6 immunoexpression for functioning pituitary macroadenomas |
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