Immunohistochemical evaluation of the mTOR pathway in intra-oral minor salivary gland neoplasms

Objectives The aim of this study was to investigate the expression of upstream and downstream molecules of the oncogenic mTOR signaling pathway in intra‐oral minor salivary gland tumors (SGTs). Materials and Methods Tissue samples consisted of 39 malignant and 13 benign minor SGTs, and 8 controls of...

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Veröffentlicht in:Oral diseases 2016-10, Vol.22 (7), p.620-629
Hauptverfasser: Diamanti, S, Nikitakis, N, Rassidakis, G, Doulis, I, Sklavounou, A
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container_issue 7
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creator Diamanti, S
Nikitakis, N
Rassidakis, G
Doulis, I
Sklavounou, A
description Objectives The aim of this study was to investigate the expression of upstream and downstream molecules of the oncogenic mTOR signaling pathway in intra‐oral minor salivary gland tumors (SGTs). Materials and Methods Tissue samples consisted of 39 malignant and 13 benign minor SGTs, and 8 controls of normal minor salivary glands (NMSG). An immunohistochemical analysis for phosphorylated Akt, 4EBP1 and S6 (total and phosphorylated), and eIF4E was performed. Results Expression of pAkt and 4EBP1 was observed in all SGTs and in most NMSG. p4EBP1 was detected in almost all SGT cases, NMSG being negative. S6 immunoreactivity was observed in 37.5% of NMSG, 92.3% of benign and 100% of malignant SGTs, while pS6 expression was observed in 77% of benign and 95% of malignant SGTs, but not in NMSG. Finally, eIF4E was expressed in 12.5% of NMSG, 69.2% of benign, and 76.9% of malignant tumors. All molecules studied had statistically significantly lower expression in NMSG compared with SGTs. Moreover, malignant neoplasms received higher scores compared with benign tumors for all molecules with the exception of eIF4E. Conclusion The mTOR signaling pathway is activated in SGTs, especially in malignancies. Therefore, the possible therapeutic role of targeting the mTOR pathway by rapamycin analogs in SGTs needs further investigation.
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Materials and Methods Tissue samples consisted of 39 malignant and 13 benign minor SGTs, and 8 controls of normal minor salivary glands (NMSG). An immunohistochemical analysis for phosphorylated Akt, 4EBP1 and S6 (total and phosphorylated), and eIF4E was performed. Results Expression of pAkt and 4EBP1 was observed in all SGTs and in most NMSG. p4EBP1 was detected in almost all SGT cases, NMSG being negative. S6 immunoreactivity was observed in 37.5% of NMSG, 92.3% of benign and 100% of malignant SGTs, while pS6 expression was observed in 77% of benign and 95% of malignant SGTs, but not in NMSG. Finally, eIF4E was expressed in 12.5% of NMSG, 69.2% of benign, and 76.9% of malignant tumors. All molecules studied had statistically significantly lower expression in NMSG compared with SGTs. Moreover, malignant neoplasms received higher scores compared with benign tumors for all molecules with the exception of eIF4E. Conclusion The mTOR signaling pathway is activated in SGTs, especially in malignancies. Therefore, the possible therapeutic role of targeting the mTOR pathway by rapamycin analogs in SGTs needs further investigation.</description><identifier>ISSN: 1354-523X</identifier><identifier>ISSN: 1601-0825</identifier><identifier>EISSN: 1601-0825</identifier><identifier>DOI: 10.1111/odi.12504</identifier><identifier>PMID: 27177463</identifier><language>eng</language><publisher>Denmark: Blackwell Publishing Ltd</publisher><subject>4E-binding protein 1 ; Adult ; Aged ; Akt ; Dentistry ; eIF4E ; Female ; Humans ; Immunohistochemistry ; intra-oral minor salivary gland neoplasms ; Medicin och hälsovetenskap ; Middle Aged ; mTOR ; Oral cancer ; Rodents ; Salivary Gland Neoplasms - metabolism ; Salivary Glands, Minor ; Signal Transduction - physiology ; TOR Serine-Threonine Kinases - analysis ; Tumors</subject><ispartof>Oral diseases, 2016-10, Vol.22 (7), p.620-629</ispartof><rights>2016 John Wiley &amp; Sons A/S. Published by John Wiley &amp; Sons Ltd</rights><rights>2016 John Wiley &amp; Sons A/S. Published by John Wiley &amp; Sons Ltd.</rights><rights>Copyright © 2016 John Wiley &amp; Sons A/S. Published by John Wiley &amp; Sons Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6484-3ac5eccbcc33d8ba861510834582108be16f5ea1ac3daae67c84437d93aefd0c3</citedby><cites>FETCH-LOGICAL-c6484-3ac5eccbcc33d8ba861510834582108be16f5ea1ac3daae67c84437d93aefd0c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fodi.12504$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fodi.12504$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27177463$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:134374329$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Diamanti, S</creatorcontrib><creatorcontrib>Nikitakis, N</creatorcontrib><creatorcontrib>Rassidakis, G</creatorcontrib><creatorcontrib>Doulis, I</creatorcontrib><creatorcontrib>Sklavounou, A</creatorcontrib><title>Immunohistochemical evaluation of the mTOR pathway in intra-oral minor salivary gland neoplasms</title><title>Oral diseases</title><addtitle>Oral Dis</addtitle><description>Objectives The aim of this study was to investigate the expression of upstream and downstream molecules of the oncogenic mTOR signaling pathway in intra‐oral minor salivary gland tumors (SGTs). Materials and Methods Tissue samples consisted of 39 malignant and 13 benign minor SGTs, and 8 controls of normal minor salivary glands (NMSG). An immunohistochemical analysis for phosphorylated Akt, 4EBP1 and S6 (total and phosphorylated), and eIF4E was performed. Results Expression of pAkt and 4EBP1 was observed in all SGTs and in most NMSG. p4EBP1 was detected in almost all SGT cases, NMSG being negative. S6 immunoreactivity was observed in 37.5% of NMSG, 92.3% of benign and 100% of malignant SGTs, while pS6 expression was observed in 77% of benign and 95% of malignant SGTs, but not in NMSG. Finally, eIF4E was expressed in 12.5% of NMSG, 69.2% of benign, and 76.9% of malignant tumors. All molecules studied had statistically significantly lower expression in NMSG compared with SGTs. Moreover, malignant neoplasms received higher scores compared with benign tumors for all molecules with the exception of eIF4E. Conclusion The mTOR signaling pathway is activated in SGTs, especially in malignancies. 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Nikitakis, N ; Rassidakis, G ; Doulis, I ; Sklavounou, A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6484-3ac5eccbcc33d8ba861510834582108be16f5ea1ac3daae67c84437d93aefd0c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>4E-binding protein 1</topic><topic>Adult</topic><topic>Aged</topic><topic>Akt</topic><topic>Dentistry</topic><topic>eIF4E</topic><topic>Female</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>intra-oral minor salivary gland neoplasms</topic><topic>Medicin och hälsovetenskap</topic><topic>Middle Aged</topic><topic>mTOR</topic><topic>Oral cancer</topic><topic>Rodents</topic><topic>Salivary Gland Neoplasms - metabolism</topic><topic>Salivary Glands, Minor</topic><topic>Signal Transduction - physiology</topic><topic>TOR Serine-Threonine Kinases - analysis</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Diamanti, S</creatorcontrib><creatorcontrib>Nikitakis, N</creatorcontrib><creatorcontrib>Rassidakis, G</creatorcontrib><creatorcontrib>Doulis, I</creatorcontrib><creatorcontrib>Sklavounou, A</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>Oral diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Diamanti, S</au><au>Nikitakis, N</au><au>Rassidakis, G</au><au>Doulis, I</au><au>Sklavounou, A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunohistochemical evaluation of the mTOR pathway in intra-oral minor salivary gland neoplasms</atitle><jtitle>Oral diseases</jtitle><addtitle>Oral Dis</addtitle><date>2016-10</date><risdate>2016</risdate><volume>22</volume><issue>7</issue><spage>620</spage><epage>629</epage><pages>620-629</pages><issn>1354-523X</issn><issn>1601-0825</issn><eissn>1601-0825</eissn><abstract>Objectives The aim of this study was to investigate the expression of upstream and downstream molecules of the oncogenic mTOR signaling pathway in intra‐oral minor salivary gland tumors (SGTs). Materials and Methods Tissue samples consisted of 39 malignant and 13 benign minor SGTs, and 8 controls of normal minor salivary glands (NMSG). An immunohistochemical analysis for phosphorylated Akt, 4EBP1 and S6 (total and phosphorylated), and eIF4E was performed. Results Expression of pAkt and 4EBP1 was observed in all SGTs and in most NMSG. p4EBP1 was detected in almost all SGT cases, NMSG being negative. S6 immunoreactivity was observed in 37.5% of NMSG, 92.3% of benign and 100% of malignant SGTs, while pS6 expression was observed in 77% of benign and 95% of malignant SGTs, but not in NMSG. Finally, eIF4E was expressed in 12.5% of NMSG, 69.2% of benign, and 76.9% of malignant tumors. All molecules studied had statistically significantly lower expression in NMSG compared with SGTs. Moreover, malignant neoplasms received higher scores compared with benign tumors for all molecules with the exception of eIF4E. Conclusion The mTOR signaling pathway is activated in SGTs, especially in malignancies. Therefore, the possible therapeutic role of targeting the mTOR pathway by rapamycin analogs in SGTs needs further investigation.</abstract><cop>Denmark</cop><pub>Blackwell Publishing Ltd</pub><pmid>27177463</pmid><doi>10.1111/odi.12504</doi><tpages>10</tpages></addata></record>
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subjects 4E-binding protein 1
Adult
Aged
Akt
Dentistry
eIF4E
Female
Humans
Immunohistochemistry
intra-oral minor salivary gland neoplasms
Medicin och hälsovetenskap
Middle Aged
mTOR
Oral cancer
Rodents
Salivary Gland Neoplasms - metabolism
Salivary Glands, Minor
Signal Transduction - physiology
TOR Serine-Threonine Kinases - analysis
Tumors
title Immunohistochemical evaluation of the mTOR pathway in intra-oral minor salivary gland neoplasms
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