ALK is frequently phosphorylated in Merkel cell carcinoma and associates with longer survival
Merkel cell carcinoma (MCC) is a rare skin cancer with only limited therapeutic options for advanced disease. We previously showed that oncogene ALK is frequently expressed at the RNA level in MCC and further that ALK positivity by immunohistochemistry is frequent and correlates strongly with Merkel...
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| creator | Jaatinen, Jenni Veija, Tuukka Salmikangas, Marko Böhling, Tom Sihto, Harri Koljonen, Virve |
| description | Merkel cell carcinoma (MCC) is a rare skin cancer with only limited therapeutic options for advanced disease. We previously showed that oncogene ALK is frequently expressed at the RNA level in MCC and further that ALK positivity by immunohistochemistry is frequent and correlates strongly with Merkel cell polyomavirus (MCPyV) positivity. In this study, we investigated whether ALK receptor is active in MCC tumor samples and MCC cell lines, and whether ALK would be a prospective treatment target in MCC. We utilized tissue microarrays constructed from 136 primary MCC tumor samples as well as nine previously established MCC cell lines to determine the presence of ALK and phosphorylated ALK (p-ALK) via immunohistochemistry. Almost half of the analyzed MCC tumors displayed ALK phosphorylation (47.8%). Analysis of MCC tumor samples revealed that the presence of p-ALK correlated to MCPyV positivity, younger age, nonexistence of metastases at diagnosis and ultimately to better MCC-specific survival. In contrast to MCC tumor samples only two out of nine MCC cell lines showed only low ALK phosphorylation by immunohistochemistry. Our study reveals clear disparity in ALK activity between patient derived tumors and cell line samples and therefore, more advanced disease models such as xenografts are necessary to resolve whether ALK is a useful treatment target in MCC. |
| doi_str_mv | 10.1371/journal.pone.0252099 |
| format | Article |
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We previously showed that oncogene ALK is frequently expressed at the RNA level in MCC and further that ALK positivity by immunohistochemistry is frequent and correlates strongly with Merkel cell polyomavirus (MCPyV) positivity. In this study, we investigated whether ALK receptor is active in MCC tumor samples and MCC cell lines, and whether ALK would be a prospective treatment target in MCC. We utilized tissue microarrays constructed from 136 primary MCC tumor samples as well as nine previously established MCC cell lines to determine the presence of ALK and phosphorylated ALK (p-ALK) via immunohistochemistry. Almost half of the analyzed MCC tumors displayed ALK phosphorylation (47.8%). Analysis of MCC tumor samples revealed that the presence of p-ALK correlated to MCPyV positivity, younger age, nonexistence of metastases at diagnosis and ultimately to better MCC-specific survival. In contrast to MCC tumor samples only two out of nine MCC cell lines showed only low ALK phosphorylation by immunohistochemistry. Our study reveals clear disparity in ALK activity between patient derived tumors and cell line samples and therefore, more advanced disease models such as xenografts are necessary to resolve whether ALK is a useful treatment target in MCC.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0252099</identifier><identifier>PMID: 34029351</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; AKT protein ; Biology and Life Sciences ; Biotechnology ; Care and treatment ; Cell cycle ; Extracellular signal-regulated kinase ; Fusion protein ; Gene expression ; Immunotherapy ; Kinases ; Lung cancer ; Lung carcinoma ; Lymphoma ; MAP kinase ; Medical prognosis ; Medicine and Health Sciences ; Merkel cell carcinoma ; Metabolic pathways ; Metastasis ; Pathology ; Phosphorylation ; Proteins ; Receptor mechanisms ; Receptors ; Research and Analysis Methods ; Skin cancer ; Statistical analysis ; Statistical methods ; Survival ; Tabulation ; Therapeutic targets ; Tumors ; Tyrosine</subject><ispartof>PloS one, 2021-05, Vol.16 (5), p.e0252099-e0252099</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Jaatinen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 Jaatinen et al 2021 Jaatinen et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c669t-5da84d33e425bc17500b7feee2fdcf807d12d166de55cee88f611fc4444979ce3</citedby><cites>FETCH-LOGICAL-c669t-5da84d33e425bc17500b7feee2fdcf807d12d166de55cee88f611fc4444979ce3</cites><orcidid>0000-0001-9603-793X ; 0000-0001-5265-5509</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143417/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143417/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids></links><search><contributor>L’Imperio, Vincenzo</contributor><creatorcontrib>Jaatinen, Jenni</creatorcontrib><creatorcontrib>Veija, Tuukka</creatorcontrib><creatorcontrib>Salmikangas, Marko</creatorcontrib><creatorcontrib>Böhling, Tom</creatorcontrib><creatorcontrib>Sihto, Harri</creatorcontrib><creatorcontrib>Koljonen, Virve</creatorcontrib><title>ALK is frequently phosphorylated in Merkel cell carcinoma and associates with longer survival</title><title>PloS one</title><description>Merkel cell carcinoma (MCC) is a rare skin cancer with only limited therapeutic options for advanced disease. We previously showed that oncogene ALK is frequently expressed at the RNA level in MCC and further that ALK positivity by immunohistochemistry is frequent and correlates strongly with Merkel cell polyomavirus (MCPyV) positivity. In this study, we investigated whether ALK receptor is active in MCC tumor samples and MCC cell lines, and whether ALK would be a prospective treatment target in MCC. We utilized tissue microarrays constructed from 136 primary MCC tumor samples as well as nine previously established MCC cell lines to determine the presence of ALK and phosphorylated ALK (p-ALK) via immunohistochemistry. Almost half of the analyzed MCC tumors displayed ALK phosphorylation (47.8%). Analysis of MCC tumor samples revealed that the presence of p-ALK correlated to MCPyV positivity, younger age, nonexistence of metastases at diagnosis and ultimately to better MCC-specific survival. In contrast to MCC tumor samples only two out of nine MCC cell lines showed only low ALK phosphorylation by immunohistochemistry. Our study reveals clear disparity in ALK activity between patient derived tumors and cell line samples and therefore, more advanced disease models such as xenografts are necessary to resolve whether ALK is a useful treatment target in MCC.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>AKT protein</subject><subject>Biology and Life Sciences</subject><subject>Biotechnology</subject><subject>Care and treatment</subject><subject>Cell cycle</subject><subject>Extracellular signal-regulated kinase</subject><subject>Fusion protein</subject><subject>Gene expression</subject><subject>Immunotherapy</subject><subject>Kinases</subject><subject>Lung cancer</subject><subject>Lung carcinoma</subject><subject>Lymphoma</subject><subject>MAP kinase</subject><subject>Medical prognosis</subject><subject>Medicine and Health Sciences</subject><subject>Merkel cell carcinoma</subject><subject>Metabolic 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rare skin cancer with only limited therapeutic options for advanced disease. We previously showed that oncogene ALK is frequently expressed at the RNA level in MCC and further that ALK positivity by immunohistochemistry is frequent and correlates strongly with Merkel cell polyomavirus (MCPyV) positivity. In this study, we investigated whether ALK receptor is active in MCC tumor samples and MCC cell lines, and whether ALK would be a prospective treatment target in MCC. We utilized tissue microarrays constructed from 136 primary MCC tumor samples as well as nine previously established MCC cell lines to determine the presence of ALK and phosphorylated ALK (p-ALK) via immunohistochemistry. Almost half of the analyzed MCC tumors displayed ALK phosphorylation (47.8%). Analysis of MCC tumor samples revealed that the presence of p-ALK correlated to MCPyV positivity, younger age, nonexistence of metastases at diagnosis and ultimately to better MCC-specific survival. In contrast to MCC tumor samples only two out of nine MCC cell lines showed only low ALK phosphorylation by immunohistochemistry. Our study reveals clear disparity in ALK activity between patient derived tumors and cell line samples and therefore, more advanced disease models such as xenografts are necessary to resolve whether ALK is a useful treatment target in MCC.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>34029351</pmid><doi>10.1371/journal.pone.0252099</doi><tpages>e0252099</tpages><orcidid>https://orcid.org/0000-0001-9603-793X</orcidid><orcidid>https://orcid.org/0000-0001-5265-5509</orcidid><oa>free_for_read</oa></addata></record> |
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| source | DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 1-Phosphatidylinositol 3-kinase AKT protein Biology and Life Sciences Biotechnology Care and treatment Cell cycle Extracellular signal-regulated kinase Fusion protein Gene expression Immunotherapy Kinases Lung cancer Lung carcinoma Lymphoma MAP kinase Medical prognosis Medicine and Health Sciences Merkel cell carcinoma Metabolic pathways Metastasis Pathology Phosphorylation Proteins Receptor mechanisms Receptors Research and Analysis Methods Skin cancer Statistical analysis Statistical methods Survival Tabulation Therapeutic targets Tumors Tyrosine |
| title | ALK is frequently phosphorylated in Merkel cell carcinoma and associates with longer survival |
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