Adipophilin expression in cutaneous malignant melanoma is associated with high proliferation and poor clinical prognosis
Adipophilin (ADP) is a primary protein component of lipid droplets (LDs). For more than half a century, certain types of cancer cells have been known to contain LDs in their cytoplasm. However, the pathological significance of ADP or LDs in cancer remains unclear. In the present study, we investigat...
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| Veröffentlicht in: | Laboratory investigation 2020-05, Vol.100 (5), p.727-737 |
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| creator | Fujimoto, Masakazu Matsuzaki, Ibu Nishitsuji, Kazuchika Yamamoto, Yuki Murakami, Daisuke Yoshikawa, Takanori Fukui, Ayaka Mori, Yuuki Nishino, Masaru Takahashi, Yuichi Iwahashi, Yoshifumi Warigaya, Kenji Kojima, Fumiyoshi Jinnin, Masatoshi Murata, Shin-ichi |
| description | Adipophilin (ADP) is a primary protein component of lipid droplets (LDs). For more than half a century, certain types of cancer cells have been known to contain LDs in their cytoplasm. However, the pathological significance of ADP or LDs in cancer remains unclear. In the present study, we investigated the association between ADP and other pathological characteristics in cutaneous malignant melanomas to clarify the role of ADP in melanoma cells. We immunostained whole paraffin sections of primary cutaneous melanomas obtained from 90 cases for ADP, after which we analyzed the correlation between ADP immunohistochemistry (IHC) and patient survival data. We also studied the relationship between the ADP IHC score and in situ hybridization (ISH) score of ADP mRNA, and the Ki67-labeling index (Ki67-LI) by using tissue microarrays consisting of 74 primary cutaneous malignant melanomas, 19 metastasizing melanomas, and 29 melanocytic nevi. Finally, we analyzed the relationship between ADP expression and cell proliferation in cutaneous melanoma cell lines. We found that high ADP expression was associated with poor metastasis-free survival, disease-specific survival, and overall survival rates of patients with cutaneous melanomas (P < 0.05). By linear regression analysis, ADP IHC was correlated with increasing ADP mRNA ISH H-scores and Ki67-LI scores in melanocytic lesions (P < 0.01). ADP IHC and ADP ISH H-scores and Ki67-LI scores were greater in pT3–4 melanomas than in pT1–2 melanomas. In cell-based assays, cells with increased ADP expression showed higher proliferation rates compared with those of low-ADP cells. Thus, ADP expression in malignant melanoma was significantly associated with high cell proliferation and poor clinical prognosis. Our results thus indicate a significant association between ADP and melanoma progression, and we propose that ADP may be a novel marker of aggressive cutaneous melanoma with a lipogenic phenotype. |
| doi_str_mv | 10.1038/s41374-019-0358-y |
| format | Article |
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For more than half a century, certain types of cancer cells have been known to contain LDs in their cytoplasm. However, the pathological significance of ADP or LDs in cancer remains unclear. In the present study, we investigated the association between ADP and other pathological characteristics in cutaneous malignant melanomas to clarify the role of ADP in melanoma cells. We immunostained whole paraffin sections of primary cutaneous melanomas obtained from 90 cases for ADP, after which we analyzed the correlation between ADP immunohistochemistry (IHC) and patient survival data. We also studied the relationship between the ADP IHC score and in situ hybridization (ISH) score of ADP mRNA, and the Ki67-labeling index (Ki67-LI) by using tissue microarrays consisting of 74 primary cutaneous malignant melanomas, 19 metastasizing melanomas, and 29 melanocytic nevi. Finally, we analyzed the relationship between ADP expression and cell proliferation in cutaneous melanoma cell lines. We found that high ADP expression was associated with poor metastasis-free survival, disease-specific survival, and overall survival rates of patients with cutaneous melanomas (P < 0.05). By linear regression analysis, ADP IHC was correlated with increasing ADP mRNA ISH H-scores and Ki67-LI scores in melanocytic lesions (P < 0.01). ADP IHC and ADP ISH H-scores and Ki67-LI scores were greater in pT3–4 melanomas than in pT1–2 melanomas. In cell-based assays, cells with increased ADP expression showed higher proliferation rates compared with those of low-ADP cells. Thus, ADP expression in malignant melanoma was significantly associated with high cell proliferation and poor clinical prognosis. Our results thus indicate a significant association between ADP and melanoma progression, and we propose that ADP may be a novel marker of aggressive cutaneous melanoma with a lipogenic phenotype.</description><identifier>ISSN: 0023-6837</identifier><identifier>EISSN: 1530-0307</identifier><identifier>DOI: 10.1038/s41374-019-0358-y</identifier><identifier>PMID: 31857696</identifier><language>eng</language><publisher>New York: Elsevier Inc</publisher><subject>13/105 ; 13/51 ; 14/63 ; 631/67/1813/1634 ; 692/699/67/1813/1634 ; Aged ; Cancer ; Cell growth ; Cell Line, Tumor ; Cell Proliferation ; Correlation analysis ; Cytoplasm ; Disease Progression ; Droplets ; Female ; Humans ; Hybridization ; Immunohistochemistry ; Laboratory Medicine ; Life Sciences & Biomedicine ; Lipids ; Male ; Markers ; Medical prognosis ; Medicine ; Medicine & Public Health ; Medicine, Research & Experimental ; Melanoma ; Melanoma - diagnosis ; Melanoma - metabolism ; Melanoma - mortality ; Melanoma - pathology ; Melanoma, Cutaneous Malignant ; Metastases ; mRNA ; Paraffin ; Paraffins ; Pathology ; Perilipin-2 - analysis ; Perilipin-2 - metabolism ; Phenotypes ; Prognosis ; Proteins ; Regression analysis ; Research & Experimental Medicine ; Science & Technology ; Skin - chemistry ; Skin - pathology ; Skin cancer ; Skin Neoplasms - diagnosis ; Skin Neoplasms - metabolism ; Skin Neoplasms - mortality ; Skin Neoplasms - pathology ; Survival</subject><ispartof>Laboratory investigation, 2020-05, Vol.100 (5), p.727-737</ispartof><rights>2019 United States & Canadian Academy of Pathology</rights><rights>The Author(s), under exclusive licence to United States and Canadian Academy of Pathology 2019</rights><rights>The Author(s), under exclusive licence to United States and Canadian Academy of Pathology 2019.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>24</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000528339200005</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c495t-a599a3837ddca4feff1c5297808c28fb9b8fcce3a719c02ec2886539e42eb0553</citedby><cites>FETCH-LOGICAL-c495t-a599a3837ddca4feff1c5297808c28fb9b8fcce3a719c02ec2886539e42eb0553</cites><orcidid>0000-0003-3056-8310 ; 0000-0001-7080-8329</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930,28253</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31857696$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fujimoto, Masakazu</creatorcontrib><creatorcontrib>Matsuzaki, Ibu</creatorcontrib><creatorcontrib>Nishitsuji, Kazuchika</creatorcontrib><creatorcontrib>Yamamoto, Yuki</creatorcontrib><creatorcontrib>Murakami, Daisuke</creatorcontrib><creatorcontrib>Yoshikawa, Takanori</creatorcontrib><creatorcontrib>Fukui, Ayaka</creatorcontrib><creatorcontrib>Mori, Yuuki</creatorcontrib><creatorcontrib>Nishino, Masaru</creatorcontrib><creatorcontrib>Takahashi, Yuichi</creatorcontrib><creatorcontrib>Iwahashi, Yoshifumi</creatorcontrib><creatorcontrib>Warigaya, Kenji</creatorcontrib><creatorcontrib>Kojima, Fumiyoshi</creatorcontrib><creatorcontrib>Jinnin, Masatoshi</creatorcontrib><creatorcontrib>Murata, Shin-ichi</creatorcontrib><title>Adipophilin expression in cutaneous malignant melanoma is associated with high proliferation and poor clinical prognosis</title><title>Laboratory investigation</title><addtitle>Lab Invest</addtitle><addtitle>LAB INVEST</addtitle><addtitle>Lab Invest</addtitle><description>Adipophilin (ADP) is a primary protein component of lipid droplets (LDs). For more than half a century, certain types of cancer cells have been known to contain LDs in their cytoplasm. However, the pathological significance of ADP or LDs in cancer remains unclear. In the present study, we investigated the association between ADP and other pathological characteristics in cutaneous malignant melanomas to clarify the role of ADP in melanoma cells. We immunostained whole paraffin sections of primary cutaneous melanomas obtained from 90 cases for ADP, after which we analyzed the correlation between ADP immunohistochemistry (IHC) and patient survival data. We also studied the relationship between the ADP IHC score and in situ hybridization (ISH) score of ADP mRNA, and the Ki67-labeling index (Ki67-LI) by using tissue microarrays consisting of 74 primary cutaneous malignant melanomas, 19 metastasizing melanomas, and 29 melanocytic nevi. Finally, we analyzed the relationship between ADP expression and cell proliferation in cutaneous melanoma cell lines. We found that high ADP expression was associated with poor metastasis-free survival, disease-specific survival, and overall survival rates of patients with cutaneous melanomas (P < 0.05). By linear regression analysis, ADP IHC was correlated with increasing ADP mRNA ISH H-scores and Ki67-LI scores in melanocytic lesions (P < 0.01). ADP IHC and ADP ISH H-scores and Ki67-LI scores were greater in pT3–4 melanomas than in pT1–2 melanomas. In cell-based assays, cells with increased ADP expression showed higher proliferation rates compared with those of low-ADP cells. Thus, ADP expression in malignant melanoma was significantly associated with high cell proliferation and poor clinical prognosis. Our results thus indicate a significant association between ADP and melanoma progression, and we propose that ADP may be a novel marker of aggressive cutaneous melanoma with a lipogenic phenotype.</description><subject>13/105</subject><subject>13/51</subject><subject>14/63</subject><subject>631/67/1813/1634</subject><subject>692/699/67/1813/1634</subject><subject>Aged</subject><subject>Cancer</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Correlation analysis</subject><subject>Cytoplasm</subject><subject>Disease Progression</subject><subject>Droplets</subject><subject>Female</subject><subject>Humans</subject><subject>Hybridization</subject><subject>Immunohistochemistry</subject><subject>Laboratory Medicine</subject><subject>Life Sciences & Biomedicine</subject><subject>Lipids</subject><subject>Male</subject><subject>Markers</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Medicine, Research & Experimental</subject><subject>Melanoma</subject><subject>Melanoma - diagnosis</subject><subject>Melanoma - metabolism</subject><subject>Melanoma - mortality</subject><subject>Melanoma - pathology</subject><subject>Melanoma, Cutaneous Malignant</subject><subject>Metastases</subject><subject>mRNA</subject><subject>Paraffin</subject><subject>Paraffins</subject><subject>Pathology</subject><subject>Perilipin-2 - analysis</subject><subject>Perilipin-2 - metabolism</subject><subject>Phenotypes</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Regression analysis</subject><subject>Research & Experimental Medicine</subject><subject>Science & Technology</subject><subject>Skin - chemistry</subject><subject>Skin - pathology</subject><subject>Skin cancer</subject><subject>Skin Neoplasms - diagnosis</subject><subject>Skin Neoplasms - metabolism</subject><subject>Skin Neoplasms - mortality</subject><subject>Skin Neoplasms - 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expression in cutaneous malignant melanoma is associated with high proliferation and poor clinical prognosis</title><author>Fujimoto, Masakazu ; Matsuzaki, Ibu ; Nishitsuji, Kazuchika ; Yamamoto, Yuki ; Murakami, Daisuke ; Yoshikawa, Takanori ; Fukui, Ayaka ; Mori, Yuuki ; Nishino, Masaru ; Takahashi, Yuichi ; Iwahashi, Yoshifumi ; Warigaya, Kenji ; Kojima, Fumiyoshi ; Jinnin, Masatoshi ; Murata, Shin-ichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c495t-a599a3837ddca4feff1c5297808c28fb9b8fcce3a719c02ec2886539e42eb0553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>13/105</topic><topic>13/51</topic><topic>14/63</topic><topic>631/67/1813/1634</topic><topic>692/699/67/1813/1634</topic><topic>Aged</topic><topic>Cancer</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Correlation analysis</topic><topic>Cytoplasm</topic><topic>Disease Progression</topic><topic>Droplets</topic><topic>Female</topic><topic>Humans</topic><topic>Hybridization</topic><topic>Immunohistochemistry</topic><topic>Laboratory Medicine</topic><topic>Life Sciences & Biomedicine</topic><topic>Lipids</topic><topic>Male</topic><topic>Markers</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Medicine, Research & Experimental</topic><topic>Melanoma</topic><topic>Melanoma - diagnosis</topic><topic>Melanoma - metabolism</topic><topic>Melanoma - mortality</topic><topic>Melanoma - pathology</topic><topic>Melanoma, Cutaneous Malignant</topic><topic>Metastases</topic><topic>mRNA</topic><topic>Paraffin</topic><topic>Paraffins</topic><topic>Pathology</topic><topic>Perilipin-2 - analysis</topic><topic>Perilipin-2 - metabolism</topic><topic>Phenotypes</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>Regression analysis</topic><topic>Research & Experimental Medicine</topic><topic>Science & Technology</topic><topic>Skin - chemistry</topic><topic>Skin - pathology</topic><topic>Skin cancer</topic><topic>Skin Neoplasms - diagnosis</topic><topic>Skin Neoplasms - metabolism</topic><topic>Skin Neoplasms - mortality</topic><topic>Skin Neoplasms - pathology</topic><topic>Survival</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fujimoto, Masakazu</creatorcontrib><creatorcontrib>Matsuzaki, Ibu</creatorcontrib><creatorcontrib>Nishitsuji, Kazuchika</creatorcontrib><creatorcontrib>Yamamoto, Yuki</creatorcontrib><creatorcontrib>Murakami, Daisuke</creatorcontrib><creatorcontrib>Yoshikawa, Takanori</creatorcontrib><creatorcontrib>Fukui, Ayaka</creatorcontrib><creatorcontrib>Mori, Yuuki</creatorcontrib><creatorcontrib>Nishino, Masaru</creatorcontrib><creatorcontrib>Takahashi, Yuichi</creatorcontrib><creatorcontrib>Iwahashi, 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Kenji</au><au>Kojima, Fumiyoshi</au><au>Jinnin, Masatoshi</au><au>Murata, Shin-ichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adipophilin expression in cutaneous malignant melanoma is associated with high proliferation and poor clinical prognosis</atitle><jtitle>Laboratory investigation</jtitle><stitle>Lab Invest</stitle><stitle>LAB INVEST</stitle><addtitle>Lab Invest</addtitle><date>2020-05-01</date><risdate>2020</risdate><volume>100</volume><issue>5</issue><spage>727</spage><epage>737</epage><pages>727-737</pages><issn>0023-6837</issn><eissn>1530-0307</eissn><abstract>Adipophilin (ADP) is a primary protein component of lipid droplets (LDs). For more than half a century, certain types of cancer cells have been known to contain LDs in their cytoplasm. However, the pathological significance of ADP or LDs in cancer remains unclear. In the present study, we investigated the association between ADP and other pathological characteristics in cutaneous malignant melanomas to clarify the role of ADP in melanoma cells. We immunostained whole paraffin sections of primary cutaneous melanomas obtained from 90 cases for ADP, after which we analyzed the correlation between ADP immunohistochemistry (IHC) and patient survival data. We also studied the relationship between the ADP IHC score and in situ hybridization (ISH) score of ADP mRNA, and the Ki67-labeling index (Ki67-LI) by using tissue microarrays consisting of 74 primary cutaneous malignant melanomas, 19 metastasizing melanomas, and 29 melanocytic nevi. Finally, we analyzed the relationship between ADP expression and cell proliferation in cutaneous melanoma cell lines. We found that high ADP expression was associated with poor metastasis-free survival, disease-specific survival, and overall survival rates of patients with cutaneous melanomas (P < 0.05). By linear regression analysis, ADP IHC was correlated with increasing ADP mRNA ISH H-scores and Ki67-LI scores in melanocytic lesions (P < 0.01). ADP IHC and ADP ISH H-scores and Ki67-LI scores were greater in pT3–4 melanomas than in pT1–2 melanomas. In cell-based assays, cells with increased ADP expression showed higher proliferation rates compared with those of low-ADP cells. Thus, ADP expression in malignant melanoma was significantly associated with high cell proliferation and poor clinical prognosis. Our results thus indicate a significant association between ADP and melanoma progression, and we propose that ADP may be a novel marker of aggressive cutaneous melanoma with a lipogenic phenotype.</abstract><cop>New York</cop><pub>Elsevier Inc</pub><pmid>31857696</pmid><doi>10.1038/s41374-019-0358-y</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-3056-8310</orcidid><orcidid>https://orcid.org/0000-0001-7080-8329</orcidid><oa>free_for_read</oa></addata></record> |
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| language | eng |
| recordid | cdi_webofscience_primary_000528339200005 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Web of Science - Science Citation Index Expanded - 2020<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" />; Alma/SFX Local Collection |
| subjects | 13/105 13/51 14/63 631/67/1813/1634 692/699/67/1813/1634 Aged Cancer Cell growth Cell Line, Tumor Cell Proliferation Correlation analysis Cytoplasm Disease Progression Droplets Female Humans Hybridization Immunohistochemistry Laboratory Medicine Life Sciences & Biomedicine Lipids Male Markers Medical prognosis Medicine Medicine & Public Health Medicine, Research & Experimental Melanoma Melanoma - diagnosis Melanoma - metabolism Melanoma - mortality Melanoma - pathology Melanoma, Cutaneous Malignant Metastases mRNA Paraffin Paraffins Pathology Perilipin-2 - analysis Perilipin-2 - metabolism Phenotypes Prognosis Proteins Regression analysis Research & Experimental Medicine Science & Technology Skin - chemistry Skin - pathology Skin cancer Skin Neoplasms - diagnosis Skin Neoplasms - metabolism Skin Neoplasms - mortality Skin Neoplasms - pathology Survival |
| title | Adipophilin expression in cutaneous malignant melanoma is associated with high proliferation and poor clinical prognosis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-15T07%3A31%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_webof&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Adipophilin%20expression%20in%20cutaneous%20malignant%20melanoma%20is%20associated%20with%20high%20proliferation%20and%20poor%20clinical%20prognosis&rft.jtitle=Laboratory%20investigation&rft.au=Fujimoto,%20Masakazu&rft.date=2020-05-01&rft.volume=100&rft.issue=5&rft.spage=727&rft.epage=737&rft.pages=727-737&rft.issn=0023-6837&rft.eissn=1530-0307&rft_id=info:doi/10.1038/s41374-019-0358-y&rft_dat=%3Cproquest_webof%3E2329740756%3C/proquest_webof%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2394145039&rft_id=info:pmid/31857696&rft_els_id=S0023683722006110&rfr_iscdi=true |