Immunohistochemical Analysis of the Metabolic Phenotype of Adrenal Cortical Carcinoma
Metabolic reprogramming is a cellular process contributing to carcinogenesis. However, it remains poorly understood in adrenal cortical carcinoma (ACC), an aggressive malignancy with overall poor prognosis and limited therapeutic options. We characterized the metabolic phenotype of ACC, by examining...
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| Veröffentlicht in: | Endocrine pathology 2020-09, Vol.31 (3), p.231-238 |
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| creator | Duan, Kai Gucer, Hasan Kefeli, Mehmet Asa, Sylvia L. Winer, Daniel A. Mete, Ozgur |
| description | Metabolic reprogramming is a cellular process contributing to carcinogenesis. However, it remains poorly understood in adrenal cortical carcinoma (ACC), an aggressive malignancy with overall poor prognosis and limited therapeutic options. We characterized the metabolic phenotype of ACC, by examining the immunoprofile of key proteins involved in glucose metabolism, hexokinase (HK1), pyruvate kinase (PKM1, PKM2), succinate dehydrogenase (SDHB), and phospho-S6 ribosomal protein (pS6), in a tissue microarray of 137 adrenal cortical tissue samples. Protein expression was compared between ACC (
n
= 42), adrenal cortical adenoma (ACA;
n
= 50), and normal adrenal cortical tissue samples (
n
= 45). Cytoplasmic expression of HK1 and PKM2 was significantly higher in ACC than in ACA (
p
|
| doi_str_mv | 10.1007/s12022-020-09624-3 |
| format | Article |
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n
= 42), adrenal cortical adenoma (ACA;
n
= 50), and normal adrenal cortical tissue samples (
n
= 45). Cytoplasmic expression of HK1 and PKM2 was significantly higher in ACC than in ACA (
p
< 0.001 and
p
= 0.014, respectively) or normal adrenal cortical tissue samples (
p
< 0.001 and
p
< 0.001, respectively). Expression of HK1 and PKM2 was also higher in ACA than in normal adrenal cortical tissue samples (
p
< 0.001 and
p
< 0.001, respectively). PKM1 expression was overall low in ACC, ACA, and normal samples, although expression of PKM1 was higher in ACC than in ACA (
p
= 0.027). There was no loss of cytoplasmic granular SDHB expression in our cohort of adrenal cortical tumors, and cytoplasmic expression of pS6 was lower in ACC than in ACA (
p
= 0.003) or normal adrenal cortical tissue samples (
p
= 0.008). Significantly, HK1 expression correlated with pyruvate kinase isoform (PKM2 and PKM1) expression (
p
< 0.001 and
p
= 0.007, respectively). Although functional validation was not performed, this study provides further evidence that metabolic reprogramming and altered glucose metabolism may occur in a subset of ACC through overexpression of intracellular glycolytic enzymes, notably HK1 and PKM2. The possibility of utilizing the reprogrammed glucose metabolism in ACC for novel therapeutic strategies should be explored in future studies.]]></description><identifier>ISSN: 1046-3976</identifier><identifier>EISSN: 1559-0097</identifier><identifier>DOI: 10.1007/s12022-020-09624-3</identifier><identifier>PMID: 32367334</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adenoma ; Carcinogenesis ; Endocrinology ; Glucose ; Glucose metabolism ; Glycolysis ; Hexokinase ; Malignancy ; Medicine ; Medicine & Public Health ; Metabolism ; Neuroendocrine tumors ; Oncology ; Pathology ; Phenotypes ; Pyruvate kinase ; Pyruvic acid ; Succinate dehydrogenase ; Tumors</subject><ispartof>Endocrine pathology, 2020-09, Vol.31 (3), p.231-238</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020</rights><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-868d75cb09ce0ed058f5e2f8e11876b9e07f25a913df9a16127b140baceeee013</citedby><cites>FETCH-LOGICAL-c375t-868d75cb09ce0ed058f5e2f8e11876b9e07f25a913df9a16127b140baceeee013</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12022-020-09624-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12022-020-09624-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32367334$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Duan, Kai</creatorcontrib><creatorcontrib>Gucer, Hasan</creatorcontrib><creatorcontrib>Kefeli, Mehmet</creatorcontrib><creatorcontrib>Asa, Sylvia L.</creatorcontrib><creatorcontrib>Winer, Daniel A.</creatorcontrib><creatorcontrib>Mete, Ozgur</creatorcontrib><title>Immunohistochemical Analysis of the Metabolic Phenotype of Adrenal Cortical Carcinoma</title><title>Endocrine pathology</title><addtitle>Endocr Pathol</addtitle><addtitle>Endocr Pathol</addtitle><description><![CDATA[Metabolic reprogramming is a cellular process contributing to carcinogenesis. However, it remains poorly understood in adrenal cortical carcinoma (ACC), an aggressive malignancy with overall poor prognosis and limited therapeutic options. We characterized the metabolic phenotype of ACC, by examining the immunoprofile of key proteins involved in glucose metabolism, hexokinase (HK1), pyruvate kinase (PKM1, PKM2), succinate dehydrogenase (SDHB), and phospho-S6 ribosomal protein (pS6), in a tissue microarray of 137 adrenal cortical tissue samples. Protein expression was compared between ACC (
n
= 42), adrenal cortical adenoma (ACA;
n
= 50), and normal adrenal cortical tissue samples (
n
= 45). Cytoplasmic expression of HK1 and PKM2 was significantly higher in ACC than in ACA (
p
< 0.001 and
p
= 0.014, respectively) or normal adrenal cortical tissue samples (
p
< 0.001 and
p
< 0.001, respectively). Expression of HK1 and PKM2 was also higher in ACA than in normal adrenal cortical tissue samples (
p
< 0.001 and
p
< 0.001, respectively). PKM1 expression was overall low in ACC, ACA, and normal samples, although expression of PKM1 was higher in ACC than in ACA (
p
= 0.027). There was no loss of cytoplasmic granular SDHB expression in our cohort of adrenal cortical tumors, and cytoplasmic expression of pS6 was lower in ACC than in ACA (
p
= 0.003) or normal adrenal cortical tissue samples (
p
= 0.008). Significantly, HK1 expression correlated with pyruvate kinase isoform (PKM2 and PKM1) expression (
p
< 0.001 and
p
= 0.007, respectively). Although functional validation was not performed, this study provides further evidence that metabolic reprogramming and altered glucose metabolism may occur in a subset of ACC through overexpression of intracellular glycolytic enzymes, notably HK1 and PKM2. The possibility of utilizing the reprogrammed glucose metabolism in ACC for novel therapeutic strategies should be explored in future studies.]]></description><subject>Adenoma</subject><subject>Carcinogenesis</subject><subject>Endocrinology</subject><subject>Glucose</subject><subject>Glucose metabolism</subject><subject>Glycolysis</subject><subject>Hexokinase</subject><subject>Malignancy</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolism</subject><subject>Neuroendocrine tumors</subject><subject>Oncology</subject><subject>Pathology</subject><subject>Phenotypes</subject><subject>Pyruvate kinase</subject><subject>Pyruvic acid</subject><subject>Succinate dehydrogenase</subject><subject>Tumors</subject><issn>1046-3976</issn><issn>1559-0097</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kE9PwyAYh4nROJ1-AQ-miefqC7SlHJfFP0tm9ODOhNK3tstaJrSHfXvZOvUmF0je5_cDHkJuKNxTAPHgKQPGYmAQg8xYEvMTckHTVMYAUpyGMyRZzKXIJuTS-zUA5QDsnEw445ngPLkgq0XbDp2tG99bU2PbGL2JZp3e7HzjI1tFfY3RK_a6sJvGRO81drbfbXE_mpUOAxnNresPubl2pulsq6_IWaU3Hq-P-5Ssnh4_5i_x8u15MZ8tY8NF2sd5lpciNQVIg4AlpHmVIqtypDQXWSERRMVSLSkvK6lpRpkoaAKFNhhW-M2U3I29W2e_BvS9WtvBhTd5xRImEyGyNAkUGynjrPcOK7V1TavdTlFQe5NqNKmCSXUwqXgI3R6rh6LF8jfyoy4AfAR8GHWf6P7u_qf2G36xfpk</recordid><startdate>20200901</startdate><enddate>20200901</enddate><creator>Duan, Kai</creator><creator>Gucer, Hasan</creator><creator>Kefeli, Mehmet</creator><creator>Asa, Sylvia L.</creator><creator>Winer, Daniel A.</creator><creator>Mete, Ozgur</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</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></search><sort><creationdate>20200901</creationdate><title>Immunohistochemical Analysis of the Metabolic Phenotype of Adrenal Cortical Carcinoma</title><author>Duan, Kai ; Gucer, Hasan ; Kefeli, Mehmet ; Asa, Sylvia L. ; Winer, Daniel A. ; Mete, Ozgur</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-868d75cb09ce0ed058f5e2f8e11876b9e07f25a913df9a16127b140baceeee013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adenoma</topic><topic>Carcinogenesis</topic><topic>Endocrinology</topic><topic>Glucose</topic><topic>Glucose metabolism</topic><topic>Glycolysis</topic><topic>Hexokinase</topic><topic>Malignancy</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolism</topic><topic>Neuroendocrine tumors</topic><topic>Oncology</topic><topic>Pathology</topic><topic>Phenotypes</topic><topic>Pyruvate kinase</topic><topic>Pyruvic acid</topic><topic>Succinate dehydrogenase</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Duan, Kai</creatorcontrib><creatorcontrib>Gucer, Hasan</creatorcontrib><creatorcontrib>Kefeli, Mehmet</creatorcontrib><creatorcontrib>Asa, Sylvia L.</creatorcontrib><creatorcontrib>Winer, Daniel A.</creatorcontrib><creatorcontrib>Mete, Ozgur</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Health & Medical Collection</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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>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><jtitle>Endocrine pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Duan, Kai</au><au>Gucer, Hasan</au><au>Kefeli, Mehmet</au><au>Asa, Sylvia L.</au><au>Winer, Daniel A.</au><au>Mete, Ozgur</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunohistochemical Analysis of the Metabolic Phenotype of Adrenal Cortical Carcinoma</atitle><jtitle>Endocrine pathology</jtitle><stitle>Endocr Pathol</stitle><addtitle>Endocr Pathol</addtitle><date>2020-09-01</date><risdate>2020</risdate><volume>31</volume><issue>3</issue><spage>231</spage><epage>238</epage><pages>231-238</pages><issn>1046-3976</issn><eissn>1559-0097</eissn><abstract><![CDATA[Metabolic reprogramming is a cellular process contributing to carcinogenesis. However, it remains poorly understood in adrenal cortical carcinoma (ACC), an aggressive malignancy with overall poor prognosis and limited therapeutic options. We characterized the metabolic phenotype of ACC, by examining the immunoprofile of key proteins involved in glucose metabolism, hexokinase (HK1), pyruvate kinase (PKM1, PKM2), succinate dehydrogenase (SDHB), and phospho-S6 ribosomal protein (pS6), in a tissue microarray of 137 adrenal cortical tissue samples. Protein expression was compared between ACC (
n
= 42), adrenal cortical adenoma (ACA;
n
= 50), and normal adrenal cortical tissue samples (
n
= 45). Cytoplasmic expression of HK1 and PKM2 was significantly higher in ACC than in ACA (
p
< 0.001 and
p
= 0.014, respectively) or normal adrenal cortical tissue samples (
p
< 0.001 and
p
< 0.001, respectively). Expression of HK1 and PKM2 was also higher in ACA than in normal adrenal cortical tissue samples (
p
< 0.001 and
p
< 0.001, respectively). PKM1 expression was overall low in ACC, ACA, and normal samples, although expression of PKM1 was higher in ACC than in ACA (
p
= 0.027). There was no loss of cytoplasmic granular SDHB expression in our cohort of adrenal cortical tumors, and cytoplasmic expression of pS6 was lower in ACC than in ACA (
p
= 0.003) or normal adrenal cortical tissue samples (
p
= 0.008). Significantly, HK1 expression correlated with pyruvate kinase isoform (PKM2 and PKM1) expression (
p
< 0.001 and
p
= 0.007, respectively). Although functional validation was not performed, this study provides further evidence that metabolic reprogramming and altered glucose metabolism may occur in a subset of ACC through overexpression of intracellular glycolytic enzymes, notably HK1 and PKM2. The possibility of utilizing the reprogrammed glucose metabolism in ACC for novel therapeutic strategies should be explored in future studies.]]></abstract><cop>New York</cop><pub>Springer US</pub><pmid>32367334</pmid><doi>10.1007/s12022-020-09624-3</doi><tpages>8</tpages></addata></record> |
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| ispartof | Endocrine pathology, 2020-09, Vol.31 (3), p.231-238 |
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| subjects | Adenoma Carcinogenesis Endocrinology Glucose Glucose metabolism Glycolysis Hexokinase Malignancy Medicine Medicine & Public Health Metabolism Neuroendocrine tumors Oncology Pathology Phenotypes Pyruvate kinase Pyruvic acid Succinate dehydrogenase Tumors |
| title | Immunohistochemical Analysis of the Metabolic Phenotype of Adrenal Cortical Carcinoma |
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