In a groundbreaking new study, researchers have unveiled a compelling link between the overexpression of the epithelial cell adhesion molecule (EpCAM) and cervical lymph node metastasis (CLNM) in papillary thyroid carcinoma (PTC). This discovery not only deepens the understanding of tumor biology in PTC but also pioneers a novel diagnostic approach combining molecular pathology with advanced imaging techniques, potentially revolutionizing preoperative risk assessment and management.
EpCAM, a transmembrane glycoprotein prominently known for its role in cell adhesion, proliferation, and differentiation, has long been recognized as a marker of epithelial tumors. Its aberrant expression has been correlated with tumor aggressiveness and poor patient prognosis across multiple cancer types. However, its precise association with loco-regional metastatic behavior in PTC—the most common form of thyroid cancer—remained elusive until now.
The study, led by Zhang et al., recruited 53 patients with clinically suspected thyroid malignancies scheduled for surgical intervention. Prior to surgery, all patients underwent a detailed ultrasonographic examination, encompassing both conventional ultrasound and contrast-enhanced ultrasound (CEUS). These imaging modalities provided comprehensive insights into nodule morphology, vascularity, and potential signs of extrathyroidal extension (ETE), an important predictor of metastatic risk.
Subsequently, postoperative tissue specimens were subjected to immunohistochemical staining to quantify EpCAM expression. Investigators meticulously analyzed the intensity and extent of EpCAM positivity, including assessments of nuclear localization—a factor implicated in transcriptional regulation and intracellular signaling pathways that might drive malignancy.
The team then dichotomized patients based on the presence or absence of cervical lymph node metastasis, aiming to identify correlations between ultrasonographic features, EpCAM expression, and metastatic status. Statistical analysis employing univariate and multivariate Cox regression models revealed that EpCAM overexpression, defined by a scoring threshold of 4.5 or higher, was strongly associated with CLNM, boasting an impressive odds ratio of 46.54. This denotes an extraordinarily high likelihood that elevated EpCAM levels predict lymphatic spread.
Notably, tumor size exceeding 1.05 cm also emerged as a significant independent predictor, with an odds ratio surpassing 14, emphasizing the continued importance of traditional morphologic measurements. Moreover, the presence of extrathyroidal extension detected through CEUS was the most potent indicator of metastasis, producing an odds ratio exceeding 113, highlighting the critical value of this imaging finding in preoperative staging.
One of the remarkable aspects of this research lies in the convergence of molecular biomarkers with cutting-edge imaging. The strong correlation between EpCAM overexpression and ultrasonographic identification of ETE underlines a multiparametric diagnostic framework, whereby molecular data refine the interpretation of imaging features to enhance clinical decision-making.
This integrated approach offers a promising avenue to stratify patients preoperatively according to metastatic risk. Such stratification is vital because it informs surgical planning—whether prophylactic lymph node dissection is warranted—and guides postoperative surveillance strategies aimed at early detection of recurrence.
Additionally, receiver operating characteristic (ROC) curve analysis demonstrated that an EpCAM score cutoff of 4.5 yielded sensitivity and specificity rates of 85.2% and 76.9%, respectively, in predicting CLNM. These robust performance metrics underscore the potential utility of EpCAM as a biomarker in routine clinical workflows, possibly even extending into non-invasive diagnostic arenas.
Encouragingly, the expression of EpCAM was also significantly associated with extrathyroidal invasion confirmed by pathology, reinforcing the hypothesis that upregulation of this molecule may drive tumor invasiveness beyond the thyroid capsule—a key factor underlying metastatic dissemination through lymphatic channels.
Interestingly, the study observed no significant difference in EpCAM expression across various histological subtypes of PTC, suggesting that its prognostic relevance transcends morphological variants and could serve as a universal indicator of aggressive disease biology.
Despite these promising outcomes, the researchers caution that further investigations involving larger patient cohorts are essential to validate these findings. In particular, the exploration of EpCAM expression in minimally invasive samples, such as fine-needle aspiration biopsy (FNAB) specimens, bears immense clinical significance. Should EpCAM profiling be feasible in FNAB material, clinicians could preoperatively identify high-risk patients and tailor therapeutic strategies accordingly.
The integration of molecular pathology with high-resolution imaging exemplified in this study aligns with the emerging paradigm of precision oncology. By transcending reliance on morphological assessments alone and incorporating molecular signatures, the medical community can advance toward more personalized and effective management of papillary thyroid carcinoma.
Moreover, the methodology employed—combining immunohistochemistry with ultrasonography—may inspire analogous diagnostic models in other epithelial cancers where EpCAM is implicated. This cross-pollination of disciplines epitomizes the future of cancer diagnostics, where imaging and molecular biology synergistically decode tumor behavior.
The findings also shed light on the pathophysiological role of EpCAM in tumor progression. Its involvement in cell adhesion and signaling pathways may facilitate tumor cell detachment, invasion, and migration, mechanistically explaining its association with lymphatic metastasis. Such mechanistic insights pave the way for targeted therapeutic interventions aimed at EpCAM or its downstream effectors.
In conclusion, the study by Zhang and colleagues represents a significant leap forward in understanding papillary thyroid carcinoma’s metastatic potential. By demonstrating that EpCAM overexpression correlates strongly with cervical lymph node metastasis and extrathyroidal extension—both critical markers of poor prognosis—they provide a compelling rationale for incorporating EpCAM assessment into preoperative evaluation protocols.
Looking ahead, this research sets the stage for multicenter clinical trials to verify the diagnostic accuracy and prognostic value of combined EpCAM-imaging approaches. Furthermore, advancements in molecular diagnostics could soon enable routine EpCAM measurement from FNAB samples, facilitating earlier and more accurate risk stratification.
Ultimately, such innovations promise to optimize patient outcomes through personalized surgical planning and follow-up, reflecting the ongoing evolution toward precision medicine in thyroid oncology. The integration of molecular biomarkers with sophisticated imaging heralds a new era where technology and biology converge to unravel the complexities of cancer metastasis with unprecedented clarity.
Subject of Research: The association between EpCAM expression and cervical lymph node metastasis in papillary thyroid carcinoma, utilizing ultrasonographic features for risk prediction.
Article Title: Correlation between EpCAM expression and cervical lymph node metastasis in papillary thyroid carcinoma: a study integrating ultrasonographic features
Article References:
Zhang, X., Li, J., Gao, M. et al. Correlation between EpCAM expression and cervical lymph node metastasis in papillary thyroid carcinoma: a study integrating ultrasonographic features. BMC Cancer 25, 803 (2025). https://doi.org/10.1186/s12885-025-14034-x
Image Credits: Scienmag.com
