{"title":"Tenascin-C作为阿霉素诱导的心肌病免疫组织病理学的潜在标志物。","authors":"Tatsuya Nishikawa, Mikio Shiba, Yoshihiko Ikeda, Keiko Ohta-Ogo, Takumi Kondo, Tomoka Tabata, Toru Oka, Wataru Shioyama, Hironori Yamamoto, Taku Yasui, Yoshiharu Higuchi, Hatsue Ishibashi-Ueda, Keiichiro Honma, Chisato Izumi, Shuichiro Higo, Kinta Hatakeyama, Yasushi Sakata, Masashi Fujita","doi":"10.1093/ehjopen/oead104","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>Doxorubicin is used in classical chemotherapy for several cancer types. Doxorubicin-induced cardiomyopathy (DOX-CM) is a critical issue among cancer patients. However, differentiating the diagnosis of DOX-CM from that of other cardiomyopathies is difficult. Therefore, in this study, we aimed to determine novel histopathological characteristics to diagnose DOX-CM.</p><p><strong>Methods and results: </strong>Twelve consecutive patients with DOX-CM who underwent cardiac histopathological examination in two medical centres were included. Twelve patients with dilated cardiomyopathy, who were matched with DOX-CM patients in terms of age, sex, and left ventricular ejection fraction, formed the control group. Another control group comprised five consecutive patients with cancer therapy-related cardiac dysfunction induced by tyrosine kinase inhibitors or vascular endothelial growth factor inhibitors were the controls. The positive area of tenascin-C, number of infiltrating macrophages, and presence of p62- and ubiquitin-positive cardiomyocytes were evaluated. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used for <i>in vitro</i> investigation. The myocardium exhibited significantly greater tenascin-C-positive area and macrophage number in the DOX-CM group than in the control groups (<i>P</i> < 0.01). The tenascin-C-positive area correlated with the number of both CD68- and CD163-positive cells (<i>r</i> = 0.748 and <i>r</i> = 0.656, respectively). Immunostaining for p62 was positive in 10 (83%) patients with DOX-CM. Furthermore, western blotting analysis revealed significant increase in tenascin-C levels in hiPSC-CMs upon doxorubicin treatment (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>The combined histopathological assessment for tenascin-C, macrophages, and p62/ubiquitin may serve as a novel tool for the diagnosis of DOX-CM. Doxorubicin may directly affect the expression of tenascin-C in the myocardium.</p>","PeriodicalId":93995,"journal":{"name":"European heart journal open","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613965/pdf/","citationCount":"0","resultStr":"{\"title\":\"Tenascin-C as a potential marker for immunohistopathology of doxorubicin-induced cardiomyopathy.\",\"authors\":\"Tatsuya Nishikawa, Mikio Shiba, Yoshihiko Ikeda, Keiko Ohta-Ogo, Takumi Kondo, Tomoka Tabata, Toru Oka, Wataru Shioyama, Hironori Yamamoto, Taku Yasui, Yoshiharu Higuchi, Hatsue Ishibashi-Ueda, Keiichiro Honma, Chisato Izumi, Shuichiro Higo, Kinta Hatakeyama, Yasushi Sakata, Masashi Fujita\",\"doi\":\"10.1093/ehjopen/oead104\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aims: </strong>Doxorubicin is used in classical chemotherapy for several cancer types. Doxorubicin-induced cardiomyopathy (DOX-CM) is a critical issue among cancer patients. However, differentiating the diagnosis of DOX-CM from that of other cardiomyopathies is difficult. Therefore, in this study, we aimed to determine novel histopathological characteristics to diagnose DOX-CM.</p><p><strong>Methods and results: </strong>Twelve consecutive patients with DOX-CM who underwent cardiac histopathological examination in two medical centres were included. Twelve patients with dilated cardiomyopathy, who were matched with DOX-CM patients in terms of age, sex, and left ventricular ejection fraction, formed the control group. Another control group comprised five consecutive patients with cancer therapy-related cardiac dysfunction induced by tyrosine kinase inhibitors or vascular endothelial growth factor inhibitors were the controls. The positive area of tenascin-C, number of infiltrating macrophages, and presence of p62- and ubiquitin-positive cardiomyocytes were evaluated. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used for <i>in vitro</i> investigation. The myocardium exhibited significantly greater tenascin-C-positive area and macrophage number in the DOX-CM group than in the control groups (<i>P</i> < 0.01). The tenascin-C-positive area correlated with the number of both CD68- and CD163-positive cells (<i>r</i> = 0.748 and <i>r</i> = 0.656, respectively). Immunostaining for p62 was positive in 10 (83%) patients with DOX-CM. Furthermore, western blotting analysis revealed significant increase in tenascin-C levels in hiPSC-CMs upon doxorubicin treatment (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>The combined histopathological assessment for tenascin-C, macrophages, and p62/ubiquitin may serve as a novel tool for the diagnosis of DOX-CM. Doxorubicin may directly affect the expression of tenascin-C in the myocardium.</p>\",\"PeriodicalId\":93995,\"journal\":{\"name\":\"European heart journal open\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-10-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613965/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European heart journal open\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/ehjopen/oead104\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/9/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European heart journal open","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/ehjopen/oead104","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/9/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
Tenascin-C as a potential marker for immunohistopathology of doxorubicin-induced cardiomyopathy.
Aims: Doxorubicin is used in classical chemotherapy for several cancer types. Doxorubicin-induced cardiomyopathy (DOX-CM) is a critical issue among cancer patients. However, differentiating the diagnosis of DOX-CM from that of other cardiomyopathies is difficult. Therefore, in this study, we aimed to determine novel histopathological characteristics to diagnose DOX-CM.
Methods and results: Twelve consecutive patients with DOX-CM who underwent cardiac histopathological examination in two medical centres were included. Twelve patients with dilated cardiomyopathy, who were matched with DOX-CM patients in terms of age, sex, and left ventricular ejection fraction, formed the control group. Another control group comprised five consecutive patients with cancer therapy-related cardiac dysfunction induced by tyrosine kinase inhibitors or vascular endothelial growth factor inhibitors were the controls. The positive area of tenascin-C, number of infiltrating macrophages, and presence of p62- and ubiquitin-positive cardiomyocytes were evaluated. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used for in vitro investigation. The myocardium exhibited significantly greater tenascin-C-positive area and macrophage number in the DOX-CM group than in the control groups (P < 0.01). The tenascin-C-positive area correlated with the number of both CD68- and CD163-positive cells (r = 0.748 and r = 0.656, respectively). Immunostaining for p62 was positive in 10 (83%) patients with DOX-CM. Furthermore, western blotting analysis revealed significant increase in tenascin-C levels in hiPSC-CMs upon doxorubicin treatment (P < 0.05).
Conclusion: The combined histopathological assessment for tenascin-C, macrophages, and p62/ubiquitin may serve as a novel tool for the diagnosis of DOX-CM. Doxorubicin may directly affect the expression of tenascin-C in the myocardium.