Epithelial Cell Adhesion Molecule Is an Accurate Target for Fluorescence Guided Imaging of Lymph Nodes

Sep 23, 2026

Lymph node excision during oncologic surgery is essential for staging and prognosis, yet surgeons face the challenge of finding all pathologically positive nodes while minimizing morbidity from removing true negative nodes. This study aimed to identify a reliable marker for intraoperative molecular imaging distinguishing lymph nodes containing non-small cell lung cancer cells from negative nodes. Epithelial Cell Adhesion Molecule (EpCAM) was assessed using immunofluorescence staining with anti-EpCAM antibody, showing markedly higher fluorescence in metastatic nodes.

LanguageEnglish

CategoryHealthcare

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Abstract

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Introduction

Molecular Imaging and Biology (2025) 27:984–992 [https://doi.org/10.1007/s1](https://doi.org/10.1007/s1) 1307-025-02058-5 Epithelial Cell Adhesion Molecule Is an Accurate Target for Fluorescence Guided Imaging of Lymph Nodes Kelly Anne McGovern1 · Katherine O. Welch1 · Ryan Krouse1 · Michael Brown1 · Lydia Chen1 · Kevin Guo1 · Jeffrey Huang1 · Jake Mlakar1 · Edward J. Delikatny2 · Viktor Gruev3 · Paul Zhang4 · Sunil Singhal1 Received: 8 June 2025 / Revised: 20 August 2025 / Accepted: 28 September 2025 / Published online: 14 October 2025 © The Author(s) 2025 Abstract Purpose Lymph node (LN) excision is critical in oncologic surgery to provide important therapeutic and diagnostic information. LN evaluation helps in staging cancers, predicting prognosis and improving survival. The ultimate wish of a surgical oncologist would be to localize and dissect all pathologically positive LNs while avoiding the morbidity of removing true negative LNs. The goal of our study was to identify a reliable marker for intraoperative molecular imaging of LNs with cancer cells from non-small cell lung cancer versus a LN without. Procedures. We identified Epithelial Cell Adhesion Molecule (EpCAM), a membrane protein normally expressed in epithelial tissues including lung. We performed immunofluorescence staining on human specimens with a conjugated anti-EpCAM monoclonal antibody. Results Fluorescence was significantly higher in LNs with metastases 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. Conclusions EpCAM may be useful for the surgical oncologist for intraoperative molecular imaging of positive LNs from lung cancer. Keywords Fluorescence-guided surgery · Lymph nodes · Lung cancer · Intraoperative molecular imaging Introduction Lymph node (LN) excision is critical in oncologic surgery to provide important therapeutic and diagnostic information. LN evaluation helps in staging cancers, predicting prognosis * Sunil Singhal [sunil.singhal@pennmedicine.upenn.edu](sunil.singhal@pennmedicine.upenn.edu) Kelly Anne McGovern [mcgovernkelly5@gmail.com](mcgovernkelly5@gmail.com) 1 Division of Thoracic Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA 2 Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA 3 Department of Engineering and Computer Engineering, University of Illinois at Urbana-Champaign, 306 N Wright St, Urbana, IL 61801, USA 4 Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA and improving survival [1–3]. The procedure for harvesting LNs during a cancer surgery varies for different cancer types such as lung, breast, gastric, colon, and thyroid. For example, in lung cancer surgery, some surgeons perform a lobe-specific approach to LN dissection, resecting only LNs contiguous to the resected lung lobe; however, using this method, 6% of patients can have missed LNs that harbor cancer cells (“positive” LNs) because they exist in non-contiguous regions [4]. Missing positive LNs results in inaccurate staging, failure to offer adjuvant treatment, and decreased survival rates. The most recent guidelines, according to the European Society of Thoracic Surgeons (ESTS), advise performing a systematic LN dissection, including at least 3 mediastinal LN stations, requiring the excision of stations 7 (subcarinal area), 10 (hilar LNs) and 11 (interlobular LNs) [5, 6] . These differences in practice highlight a major challenge for surgical oncologists to intraoperatively identify LNs that harbor cancer cells. The ultimate wish of a surgical oncologist would be to localize and dissect all positive LNs while avoiding the morbidity of removing true negative LNs. However, this isnot possible because positive and negative LNs have similar color, shape

FAQs

Why is accurate lymph node evaluation important in oncologic surgery?

Lymph node evaluation supports cancer staging, prognosis, and survival improvement. The goal is to localize all pathologically positive nodes while avoiding unnecessary removal of true negative nodes.

What marker did the study evaluate for intraoperative molecular imaging?

The study identified EpCAM (Epithelial Cell Adhesion Molecule) and assessed it using immunofluorescence staining on human specimens with a conjugated anti-EpCAM monoclonal antibody.

What were the main findings regarding fluorescence signal in lymph nodes?

Fluorescence was significantly higher in lymph nodes with metastases compared with non-metastatic nodes. The increased signal was observed in hilar and mediastinal nodes and across primary tumor histologies.

Sep 23, 2026

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