{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T15:22:43Z","timestamp":1772551363570,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015326","name":"NIH","doi-asserted-by":"publisher","award":["P01 CA254859"],"award-info":[{"award-number":["P01 CA254859"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"publisher"}]},{"name":"T32","award":["CA251063-05"],"award-info":[{"award-number":["CA251063-05"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Lymph node (LN) dissection is a necessary part of every oncologic surgery in order to provide important information for staging, predicting prognosis and improving survival. To do this, surgical oncologists strive to localize and dissect every pathologically positive LN while avoiding the increased morbidity of removing true negative LNs. The goal is to develop an imaging method to distinguish positive and negative LNs, but a specific biomarker is missing. Thus, our aim is to identify a reliable imaging marker for identifying LNs with lung cancer cells. After screening many epithelial markers, we identified E-cadherin, a membrane protein normally expressed in epithelial cells, including in the lung. To follow up on our potential target, we performed immunofluorescence staining on 48 human LNs with a conjugated anti-E-cadherin monoclonal antibody. Fluorescence was significantly higher in LNs with metastasis, as shown in 48 positive LNs from patients with resected primary lung cancer. There was high fluorescence in both hilar and mediastinal LNs, and in all primary tumor histologies. E-cadherin may be useful for the surgical oncologist for targeted imaging technologies for selecting positive LNs from lung cancer.<\/jats:p>","DOI":"10.3390\/cimb48030268","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T09:45:12Z","timestamp":1772531112000},"page":"268","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["E-Cadherin Is an Accurate Target for Fluorescence-Guided Imaging of Lymph Nodes"],"prefix":"10.3390","volume":"48","author":[{"given":"Kelly A.","family":"McGovern","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine O.","family":"Welch","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7950-8930","authenticated-orcid":false,"given":"Jake","family":"Mlakar","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8350-1717","authenticated-orcid":false,"given":"Ryan","family":"Krouse","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lydia","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6989-5611","authenticated-orcid":false,"given":"Kevin","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward J.","family":"Delikatny","sequence":"additional","affiliation":[{"name":"Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viktor","family":"Gruev","sequence":"additional","affiliation":[{"name":"Department of Engineering and Computer Engineering, University of Illinois at Urbana-Champaign, 306 N Wright St, Urbana, IL 61801, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2413-7082","authenticated-orcid":false,"given":"Sunil","family":"Singhal","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1097\/01.sla.0000086543.45557.cb","article-title":"Lymphatic Mapping and Sentinel Lymphadenectomy for Early-Stage Melanoma: Therapeutic Utility and Implications of Nodal Microanatomy and Molecular Staging for Improving the Accuracy of Detection of Nodal Micrometastases","volume":"238","author":"Morton","year":"2003","journal-title":"Ann. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1245\/ASO.2003.03.058","article-title":"The Prognosis of T3N0 Colon Cancer Is Dependent on the Number of Lymph Nodes Examined","volume":"10","author":"Swanson","year":"2003","journal-title":"Ann. Surg. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2912","DOI":"10.1200\/JCO.2011.40.3519","article-title":"Sentinel Lymph Node Biopsy for Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Joint Clinical Practice Guideline","volume":"30","author":"Wong","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.lungcan.2010.02.009","article-title":"Subcarinal lymph node in upper lobe non-small cell lung cancer patients: Is selective lymph node dissection valid?","volume":"70","author":"Aokage","year":"2010","journal-title":"Lung Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.ejcts.2006.08.008","article-title":"ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer","volume":"30","author":"Lardinois","year":"2006","journal-title":"Eur. J. Cardio-Thorac. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.athoracsur.2005.06.066","article-title":"Morbidity and Mortality of Major Pulmonary Resections in Patients with Early-Stage Lung Cancer: Initial Results of the Randomized, Prospective ACOSOG Z0030 Trial","volume":"81","author":"Allen","year":"2006","journal-title":"Ann. Thorac. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1002\/jso.25149","article-title":"Intraoperative fluorescence imaging in thoracic surgery","volume":"118","author":"Newton","year":"2018","journal-title":"J. Surg. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.3171\/2015.5.JNS1577","article-title":"A prospective Phase II clinical trial of 5-aminolevulinic acid to assess the correlation of intraoperative fluorescence intensity and degree of histologic cellularity during resection of high-grade gliomas","volume":"124","author":"Lau","year":"2016","journal-title":"J. Neurosurg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4769","DOI":"10.1038\/s41388-018-0304-2","article-title":"E-cadherin in contact inhibition and cancer","volume":"37","author":"Mendonsa","year":"2018","journal-title":"Oncogene"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.cell.2011.09.024","article-title":"Tumor Metastasis: Molecular Insights and Evolving Paradigms","volume":"147","author":"Valastyan","year":"2011","journal-title":"Cell"},{"key":"ref_11","first-page":"1659","article-title":"Significance and prognosis of epithelial-cadherin expression in invasive breast carcinoma","volume":"16","author":"Yang","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1146\/annurev-cellbio-092910-154036","article-title":"The ins and outs of the epithelial to mesenchymal transition in health and disease","volume":"27","author":"Nieto","year":"2011","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/35000025","article-title":"The transcription factor Snail controls epithelial\u2013mesenchymal transitions by repressing E-cadherin expression","volume":"2","author":"Cano","year":"2000","journal-title":"Nat. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1164\/ajrccm.157.4.9703099","article-title":"Reduced E-cadherin expression is associated with increased lymph node metastasis and unfavorable prognosis in non-small cell lung cancer","volume":"157","author":"Sulzer","year":"1998","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1016\/S0022-5347(05)66330-6","article-title":"E-cadherin immunostaining of bladder transitional cell carcinoma, carcinoma in situ and lymph node metastases with long-term followup","volume":"165","author":"Byrne","year":"2001","journal-title":"J. Urol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"107341","DOI":"10.1016\/j.lungcan.2023.107341","article-title":"Impact of skip mediastinal lymph node metastasis on outcomes after resection for primary lung cancer","volume":"184","author":"Taylor","year":"2023","journal-title":"Lung Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wang, X., Guo, H., Hu, Q., Ying, Y., and Chen, B. (2021). The Impact of Skip vs. Non-Skip N2 Lymph Node Metastasis on the Prognosis of Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. Front. Surg., 8.","DOI":"10.3389\/fsurg.2021.749156"},{"key":"ref_19","first-page":"e58577","article-title":"Exploring the Diagnostic Challenges of Uterine Lesions in Frozen Section: A Comprehensive Study at a Tertiary Care Center","volume":"16","author":"Neelayadakshi","year":"2024","journal-title":"Cureus"},{"key":"ref_20","first-page":"4","article-title":"Intra-operative frozen section consultation: Concepts, applications and limitations","volume":"13","author":"Jaafar","year":"2006","journal-title":"Malays. J. Med. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.1007\/s00259-023-06141-3","article-title":"Prospective validation of tumor folate receptor expression density with the association of pafolacianine fluorescence during intraoperative molecular imaging-guided lung cancer resections","volume":"50","author":"Azari","year":"2023","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/j.athoracsur.2014.05.026","article-title":"Intraoperative near-infrared imaging can identify pulmonary nodules","volume":"98","author":"Okusanya","year":"2014","journal-title":"Ann. Thorac. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e468","DOI":"10.1016\/j.jtcvs.2023.02.025","article-title":"Pafolacianine for intraoperative molecular imaging of cancer in the lung: The ELUCIDATE trial","volume":"166","author":"Sarkaria","year":"2023","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1001\/jamasurg.2022.1075","article-title":"Clinical Impact of Intraoperative Margin Assessment in Breast-Conserving Surgery with a Novel Pegulicianine Fluorescence-Guided System: A Nonrandomized Controlled Trial","volume":"157","author":"Hwang","year":"2022","journal-title":"JAMA Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1200\/JCO.22.00291","article-title":"A Phase III Study of Pafolacianine Injection (OTL38) for Intraoperative Imaging of Folate Receptor-Positive Ovarian Cancer (Study 006)","volume":"41","author":"Tanyi","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zeh, R., Sheikh, S., Xia, L., Pierce, J., Newton, A., Predina, J., Cho, S., Nasrallah, M., Singhal, S., and Dorsey, J. (2017). The second window ICG technique demonstrates a broad plateau period for near infrared fluorescence tumor contrast in glioblastoma. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0182034"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1227\/NEU.0000000000001450","article-title":"Intraoperative Near-Infrared Optical Imaging Can Localize Gadolinium-Enhancing Gliomas During Surgery","volume":"79","author":"Lee","year":"2016","journal-title":"Neurosurgery"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/s11307-022-01768-4","article-title":"Cysteine Cathepsins in Breast Cancer: Promising Targets for Fluorescence-Guided Surgery","volume":"25","author":"Linders","year":"2023","journal-title":"Mol. Imaging Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5447290","DOI":"10.1155\/2022\/5447290","article-title":"Preclinical Evaluation of an Activity-Based Probe for Intraoperative Imaging of Esophageal Cancer","volume":"2022","author":"Kennedy","year":"2022","journal-title":"Mol. Imaging"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s10549-018-4845-4","article-title":"Real-time, intraoperative detection of residual breast cancer in lumpectomy cavity walls using a novel cathepsin-activated fluorescent imaging system","volume":"171","author":"Smith","year":"2018","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1111\/j.1600-6143.2006.01469.x","article-title":"Intraoperative detection of cell injury and cell death with an 800 nm near-infrared fluorescent annexin V derivative","volume":"6","author":"Ohnishi","year":"2006","journal-title":"Am. J. Transplant."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/3\/268\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T12:05:58Z","timestamp":1772539558000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/3\/268"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,3]]},"references-count":31,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["cimb48030268"],"URL":"https:\/\/doi.org\/10.3390\/cimb48030268","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,3]]}}}