{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T22:55:18Z","timestamp":1776898518691,"version":"3.51.2"},"reference-count":47,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T00:00:00Z","timestamp":1686873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dermatopathology"],"abstract":"<jats:p>Background: Granular cell tumors (GCT) are rare neoplasms of Schwann cell origin occurring in the skin and in other organs. The etiopathogenesis of GCT is yet poorly understood. Connexin 43 (Cx43) is the most broadly expressed gap junction protein in humans, the tumoral role of which has been investigated in several types of tumors. Its role in GCT of the skin, oral cavity and gastrointestinal tract is as yet unknown. Methods: Herein, we present a study on the immunohistochemical expression of Cx43 in GCT of the skin (n = 15), tongue (n = 4) and esophagus (n = 3). Immunolabeling was scored positive (weak (+), moderate (++) or strong (+++)). Results: Cx43 was expressed by all cases of GCT of the skin, tongue and esophagus (22\/22), showing moderate to strong staining. All tissue sections of GCT were characterized by a diffuse, cytoplasmic staining pattern of the tumor cells. None of those showed membranous or nuclear staining. Conclusion: Our results suggest that Cx43 probably plays an important role in the development of this rare tumor entity.<\/jats:p>","DOI":"10.3390\/dermatopathology10020026","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T03:24:58Z","timestamp":1686885898000},"page":"184-192","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Expression of Connexin 43 in Granular Cell Tumors of the Skin, Tongue and Esophagus"],"prefix":"10.3390","volume":"10","author":[{"given":"Hermann","family":"Kneitz","sequence":"first","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Verena","family":"Frings","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Kircher","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7095-9848","authenticated-orcid":false,"given":"Matthias","family":"Goebeler","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4429","DOI":"10.1038\/s41388-019-0741-6","article-title":"Connexins in cancer: Bridging the gap to the clinic","volume":"38","author":"Aasen","year":"2019","journal-title":"Oncogene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1080\/09687680210139839","article-title":"Gap junctions: Structure and function","volume":"19","author":"Evans","year":"2002","journal-title":"Mol. Membr. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"192","DOI":"10.3389\/fmed.2019.00192","article-title":"Connexin43 as a Tumor Suppressor: Proposed Connexin43 mRNA-circularRNAs-microRNAs Axis Towards Prevention and Early Detection in Breast Cancer","volume":"6","author":"Talhouk","year":"2019","journal-title":"Front. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12964-022-01009-9","article-title":"The roles of connexins and gap junctions in the progression of cancer","volume":"21","author":"Zhou","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/nrc.2016.105","article-title":"Gap junctions and cancer: Communicating for 50\u2009years","volume":"16","author":"Aasen","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_6","first-page":"941","article-title":"Selective in situ protein expression profiles correlate with distinct phenotypes of basal cell carcinoma and squamous cell carcinoma of the skin","volume":"28","author":"Stelkovics","year":"2013","journal-title":"Hist. Histopath."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1097\/DAD.0b013e318278d401","article-title":"Melanocytic tumors express connexin 43 but not 26: Immunohistochemical analysis with potential significance in melanocytic oncogenesis","volume":"35","author":"Sargen","year":"2013","journal-title":"Am. J. Dermatopathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1097\/DAD.0000000000001395","article-title":"Expression of Connexin 43 (Cx43) in benign Cutaneous Tumors with Follicular Differentiation","volume":"41","author":"Mayan","year":"2019","journal-title":"Am. J. Dermatopathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5437","DOI":"10.21873\/anticanres.11122","article-title":"CX43 Expression in Colonic Adenomas and Surrounding Mucosa Is a Marker of Malignant Potential","volume":"36","author":"Boban","year":"2016","journal-title":"Anticancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.3892\/ijo.2017.4114","article-title":"Connexin 43 in the development and progression of breast cancer: What\u2019s the connection?","volume":"51","author":"Phillips","year":"2017","journal-title":"Int. J. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1007\/s12105-016-0685-x","article-title":"Connexin 43 (Cx43) Expression in Laryngeal Squamous Cell Carcinomas: Preliminary Data on Its Possible Prognostic Role","volume":"10","author":"Puzzo","year":"2016","journal-title":"Head Neck Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1111\/cup.14066","article-title":"Aberrant cytoplasmic connexin43 expression as a helpful marker in vascular neoplasms","volume":"48","author":"Frings","year":"2021","journal-title":"J. Cutan. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/BF02078314","article-title":"\u00dcber Myome ausgehend von der quergestreiften willk\u00fcrlichen Muskulatur (On myomas originating from cross-striated voluntary muscle)","volume":"260","author":"Abrikossoff","year":"1926","journal-title":"Virchows Arch. A Pathol. Anat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"152865","DOI":"10.1016\/j.prp.2020.152865","article-title":"Granular cell tumor a study of 42 cases and systemic review of the literature","volume":"216","author":"Mobarki","year":"2020","journal-title":"Pathol. Res. Pract."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"765927","DOI":"10.1155\/2009\/765927","article-title":"Granular cell tumours: A rare entity in the musculoskeletal system","volume":"2009","author":"Rose","year":"2009","journal-title":"Sarcoma"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1007\/s002560050204","article-title":"Intramuscular malignant granular cell tumor","volume":"26","author":"Tsuchida","year":"1997","journal-title":"Skelet. Radiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"132","DOI":"10.4103\/0974-2077.85039","article-title":"Subcutaneous granular cell tumour of the lumber region","volume":"4","author":"Fragulidis","year":"2011","journal-title":"J. Cutan. Aesthet. Surg."},{"key":"ref_18","first-page":"343","article-title":"Multiple cutaneous granular cell tumors: A case report and review of the literature","volume":"69","author":"Gross","year":"2002","journal-title":"Cutis"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/jso.2930130405","article-title":"Granular cell tumor: A clinicopathologic study of 110 patients","volume":"13","author":"Lack","year":"1980","journal-title":"J. Surg. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1186\/1477-7819-10-204","article-title":"Granular cell tumors: A report of six cases","volume":"10","author":"Aoyama","year":"2012","journal-title":"World J. Surg. Oncol."},{"key":"ref_21","first-page":"e782","article-title":"Esophageal Granular Cell Tumor: A Case Report and Review of Literature","volume":"8","author":"Nishitha","year":"2016","journal-title":"Cureus"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.anndiagpath.2010.01.005","article-title":"Morphologic spectrum, immunohistochemical analysis and clinical features of a series of granular cell tumors of soft tissues: A study from a tertiary referral cancer center","volume":"14","author":"Rekhi","year":"2010","journal-title":"Ann. Diagn. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1159\/000445479","article-title":"Slowly Growing Nodule on the Trunk: Cutaneous Granular Cell Tumor","volume":"3","author":"Erkin","year":"2016","journal-title":"Dermatopathology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1093\/ajcp\/79.1.37","article-title":"An immunoperoxidase investigation of S-100 protein in granular cell myoblastomas: Evidence for Schwann cell derivation","volume":"79","author":"Armin","year":"1983","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1097\/01.pas.0000157294.55796.d3","article-title":"Primitive nonneural granular cell tumors of skin: Clinicopathologic analysis of 13 cases","volume":"29","author":"Lazar","year":"2005","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s00428-011-1104-z","article-title":"Immunohistochemical localization of autophagosomal membrane-associated protein LC3 in granular cell tumor and schwannoma","volume":"459","author":"Shintaku","year":"2011","journal-title":"Virchows Arch."},{"key":"ref_27","first-page":"888","article-title":"Immunoreactivity of S100 protein, alpha-1-antitrypsin, and CD68 in adult and congenital granular cell tumors","volume":"9","author":"Filie","year":"1996","journal-title":"Mod. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1136\/jcp.2005.029272","article-title":"Increased expression of connexins 26 and 43 in lymph node metastases of breast cancer","volume":"59","author":"Sulkowski","year":"2006","journal-title":"J. Clin. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/1756-9966-29-79","article-title":"Clinical significance of the expression of connexin26 in colorectal cancer","volume":"29","author":"Nomura","year":"2010","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.leukres.2009.10.013","article-title":"Up-regulation of Cx43 expression and GJIC function in acute leukemia bone marrow stromal cells post-chemotherapy","volume":"34","author":"Liu","year":"2010","journal-title":"Leuk. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.canlet.2006.12.024","article-title":"Connexin 43 expression promotes malignancy of HuH7 hepatocellular carcinoma cells via the inhibition of cell-cell communication","volume":"252","author":"Zhang","year":"2007","journal-title":"Cancer Lett."},{"key":"ref_32","first-page":"4200","article-title":"The correlation between aberrant connexin 43 mRNA expression induced by promoter methylation and nodal micrometastasis in non-small cell lung cancer","volume":"9","author":"Chen","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1002\/ijc.2910560116","article-title":"Altered homologous and heterologous gap-junctional intercellular communication in primary human liver tumors associated with aberrant protein localization but not gene mutation of connexin 32","volume":"56","author":"Krutovskikh","year":"1994","journal-title":"Int. J. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/sj.onc.1203340","article-title":"Differential effect of subcellular localization of communication impairing gap junction protein connexin43 on tumor cell growth in vivo","volume":"19","author":"Krutovskikh","year":"2000","journal-title":"Oncogene"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1007\/s12032-010-9492-5","article-title":"Expression and significance of Cx43 and E-cadherin in gastric cancer and metastatic lymph nodes","volume":"28","author":"Tang","year":"2011","journal-title":"Med. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"352","DOI":"10.5114\/aoms.2020.92859","article-title":"Ultrastructure of gap junction and Cx43 expression in gastric cancer tissues of the patients","volume":"16","author":"Li","year":"2020","journal-title":"Arch. Med. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1007\/s12032-009-9354-1","article-title":"Clinical significance of vascular endothelial growth factor and connexin43 for predicting pancreatic cancer clinicopathologic parameters","volume":"27","author":"Liang","year":"2010","journal-title":"Med. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kazan, J.M., El-Saghir, J., Saliba, J., Shaito, A., Jalaleddine, N., El-Hajjar, L., Al-Ghadban, S., Yehia, L., Zibara, K., and El-Sabban, M. (2019). Cx43 expression correlates with breast cancer metastasis in MDA-MB-231 cells in vitro, in a mouse xenograft model and in human breast cancer tissues. Cancers, 11.","DOI":"10.3390\/cancers11040460"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e13055","DOI":"10.7717\/peerj.13055","article-title":"Expression of connexin-43 in surgical resections of primary tumor and lymph node metastases of squamous cell carcinoma and adenocarcinoma of the lung: A retrospective study","volume":"10","author":"Savic","year":"2022","journal-title":"PeerJ"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/cup.13856","article-title":"Expression of connexin 43 by atypical fibroxanthoma","volume":"48","author":"Mayan","year":"2021","journal-title":"J. Cutan. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/978-1-4939-3664-9_4","article-title":"Immunohisto- and Cytochemistry Analysis of Connexins","volume":"Volume 1437","author":"Cogliati","year":"2016","journal-title":"Methods in Molecular Biology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1053\/hupa.2002.123545","article-title":"Diagnosis of gastrointestinal stromal tumors: A consensus approach","volume":"33","author":"Fletcher","year":"2002","journal-title":"Hum. Pathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"30005","DOI":"10.1074\/jbc.M300614200","article-title":"Lysosomal and proteasomal degradation play distinct roles in the life cycle of Cx43 in gap junctional intercellular communication-deficient and -competent breast tumor cells","volume":"278","author":"Qin","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1083\/jcb.201710161","article-title":"Desmoplakin maintains gap junctions by inhibiting Ras\/MAPK and lysosomal degradation of connexin-43","volume":"217","author":"Kam","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"433","DOI":"10.3109\/15419060109080766","article-title":"Aggregated DsRed-tagged Cx43 and over-expressed Cx43 are targeted to lysosomes in human breast cancer cells","volume":"8","author":"Qin","year":"2001","journal-title":"Cell Commun. Adhes."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3533","DOI":"10.1038\/s41467-018-05886-y","article-title":"Loss-of-function mutations in ATP6AP1 and ATP6AP2 in granular cell tumors","volume":"9","author":"Pareja","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/gcc.22727","article-title":"Frequent mutations of genes encoding vacuolar H+-ATPase components in granular cell tumors","volume":"58","author":"Sekimizu","year":"2019","journal-title":"Genes Chromosomes Cancer"}],"container-title":["Dermatopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2296-3529\/10\/2\/26\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:56:12Z","timestamp":1760126172000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2296-3529\/10\/2\/26"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,16]]},"references-count":47,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["dermatopathology10020026"],"URL":"https:\/\/doi.org\/10.3390\/dermatopathology10020026","relation":{},"ISSN":["2296-3529"],"issn-type":[{"value":"2296-3529","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,16]]}}}