Myofibroblasts are responsible for the desmoplastic reaction surrounding human pancreatic carcinomas

Abstract

Background. The cell type responsible for the desmoplastic reaction surrounding human pancreatic carcinoma is unknown. Hepatic stellate cells, which activate to a myofibroblast-like form, are responsible for collagen deposition in cirrhosis and around hepatocellular carcinomas. Recently, pancreatic stellate cells have been described and implicated in the fibrosis of chronic pancreatitis. We sought to determine whether these cells are responsible for the scirrhous reaction surrounding pancreatic adenocarcinomas. Methods. Archival formalin-fixed, paraffin-embedded pancreatic tissues from 10 patients undergoing pancreaticoduodenectomy for ductal adenocarcinoma and from 2 patients with pancreatic islet cell tumors were examined immunohistochemically for alpha-smooth muscle actin (α-SMA), smooth muscle myosin heavy chain (SMMHC), procollagen I, collagen IV, and endothelial cell markers, von Willebrand factor and cluster of differentiation 31. Results. In non-neoplastic areas, staining for α-SMA and SMMHC was confined to interlobular septal regions. In contrast, the desmoplastic reaction surrounding all 10 pancreatic adenocarcinoma specimens displayed intense interstitial staining for α-SMA, SMMHC, and collagen IV but no staining for von Willebrand factor and cluster of differentiation 31. Procollagen I staining localized intracellularly to fibroblast-shaped cells within this α-SMA/SMMHC-positive scirrhous region. Islet cell tumors demonstrated an increase in α-SMA staining, although this was not as marked as in ductal adenocarcinomas. Conclusions. A massive increase in myofibroblast activity, compatible with the activation of stellate cells, is associated with the deposition of collagen types I and IV in the desmoplastic reaction around pancreatic adenocarcinomas.