Re-expression of embryonic stem cell markers in malignant tissue: an observational study in pancreatic cancer

Pancreatic cancer is one of the most lethal malignancies, primarily due to late-stage diagnosis and limited therapeutic options. Cancer stem cells (CSCs) contribute to tumor heterogeneity, therapy resistance, and recurrence through activation of developmental pathways such as Hedgehog, Wnt, Notch, JAK-STAT, and Hippo. Identifying CSCs is therefore essential for understanding pancreatic ductal adenocarcinoma (PDAC) pathogenesis and advancing targeted therapies. This study compares the expression of key CSC-associated markers (CD44, CD117, OCT3/4, and c-Myc) in PDAC, fetal, and adult pancreas to elucidate CSC dynamics. Immunohistochemistry for CSC markers (CD44, CD117, OCT3/4, and c-Myc) was performed on PDAC tissues and control pancreatic samples (fetal pancreas 28-36 weeks and adult pancreas) to evaluate marker expression. Proliferative potential was assessed using CK7 and Ki-67 expression patterns. CD44 showed strong membranous and cytoplasmic expression in PDAC, moderate in fetal pancreas (epithelial/ductal regions), and minimal expression in adult tissue. CD117 was mainly restricted to stromal cells in PDAC, also present in fetal tissue but low in adults. c-Myc and Ki-67 were moderately expressed in PDAC, significantly higher than the control samples. CK7 demonstrated strong cytoplasmic staining in PDAC, moderate expression in adults, and weak expression in fetal samples. CD44 and c-Myc re-expression in PDAC supports their role as CSC-associated markers and potential drivers of tumor progression. CD117's stromal localization suggests tumor-stroma interactions. These findings highlight developmental reactivation of CSC markers in PDAC, with implications for early detection and targeted therapy.