Case Report: E-cadherin and Vimentin expression in advanced-stage pancreatic ductal adenocarcinoma tissue and circulating tumor cells: preliminary results from a pilot study.

BACKGROUND

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis due to late diagnosis and early metastasis. The lack of robust biomarkers necessitates new strategies to stratify high-risk patients. Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is the gold standard for tissue acquisition. Concurrently, circulating tumor cells (CTCs) offer a non-invasive tool for prognostic assessment, specifically regarding the epithelial-to-mesenchymal transition (EMT). The loss of E-cadherin and the expression of Vimentin are key hallmarks of this transition, facilitating a metastatic phenotype and CTC survival.

AIM AND

OBJECTIVES

This retrospective, preliminary pilot study of 11 patients with advanced PDAC at onset aimed to investigate the expression of EMT markers in EUS-FNB tissue biopsies. Concurrently, we characterized EMT profiles across isolated PDAC CTCs comprising -CD45-EPCAM+CD74+, CD45-EPCAM-CD74+, and CD45-EPCAM+CD74- subpopulations-from the same patients. The inclusion of CD74-positive cells was prioritized due to the role of CD74 not only as an invasive marker but also as a functional driver of the epithelial-mesenchymal transition in cancer.

METHODS

EUS-FNB was performed for histological diagnosis and IHC analysis of E-cadherin and Vimentin in 11 PDAC samples (grade G1-G3). Concurrently, CTC subpopulations were isolated via immunomagnetic CD45 depletion and EpCAM/CD74 enrichment. E-cadherin and Vimentin transcript levels in CTCs were then quantified using real-time PCR.

RESULTS

Among the 11 PDAC EUS-FNB biopsies, E-cadherin expression was absent in three cases, all of which were G3 tumors. The majority of samples (72.7%) exhibited low-to-moderate E-cadherin positivity. Regarding Vimentin, biopsies were generally negative, with the exception of small tumor cell clusters (<5%) identified in G3 samples. In contrast, E-cadherin transcripts were not detected in the corresponding CTC subpopulations. Vimentin expression was observed in the majority of CTC samples (81.8%), with nine cases showing moderate-to-high levels and the remaining two cases exhibiting faint expression.

CONCLUSIONS

Our assay demonstrated a potentially favorable performance, highlighting distinct EMT expression between the primary tumor and CTCs. This baseline comparison of EMT markers in matched PDAC samples and CTCs underscores the significance of mesenchymal-invasive profiles, despite the limited cohort size.