Pancreatic ductal
adenocarcinoma (PDAC) is characterized by an extensive stroma being also present in
chronic pancreatitis (CP). Using immunohistochemistry, the stroma of CP and PDAC was comprehensively analyzed and correlated with epithelial/
carcinoma-related alterations and clinicopathological patient characteristics. While there were no significant differences between CP and PDAC regarding the distribution of CD3+ T cells and α-SMA+ fibroblasts, proportions of CD4+ and CD8+ T cells were significantly lower and numbers of CD25+(CD4+) and FoxP3+(CD4+) regulatory T cells were greater in PDAC compared with CP. Macrophages were more prevalent in CP, but localized more closely to
carcinoma cells in PDAC, as were γδ-T cells. Duct-related FoxP3 and
L1CAM expression increased from CP to PDAC, while
vimentin expression was similarly abundant in both diseases. Moreover, stromal and epithelial compartments of well-differentiated
tumors and CPs shared considerable similarities, while moderately and poorly differentiated
tumors significantly differed from CP tissues. Analysis of 27 parameters within each
pancreatic disease revealed a significant correlation of i) CD4+ and FoxP3+CD4+ T cells with FoxP3 expression in PDAC cells, ii) α-SMA+ fibroblasts with
L1CAM expression and proliferation in PDAC cells, iii) CD3 and CD8 expression with γδ-TCR expression in both
pancreatic diseases and iv) CD68+ and CD163+ macrophages with
vimentin expression in PDAC cells. High expression of FoxP3,
vimentin and
L1CAM in PDAC cells as well as a
tumor-related localization of macrophages each tended to correlate with higher
tumor grade. Multivariate survival analysis revealed a younger age at time of surgery as a positive prognostic marker for PDAC patients with the most frequently operated disease stage T3N1M0. Overall this study identified several interrelationships between stroma and epithelial/
carcinoma cells in PDACs but also in CP, which in light of previous experimental data strongly support the view that the inflammatory stroma contributes to
malignancy-associated alterations already in precursor cells during CP.