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: 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.