Histone H3 MRNA in situ hybridization for identifying proliferating cells in human pancreas, with special reference to the ductal system

In general, the incidence of proliferating cells parallels that of carcinogenesis. We have investigated proliferating activity and phenotype expression in epithelial cells in normal tissue, mucinous metaplasia and ductal adenocarcinoma of the pancreas. Twenty-eight resected pancreases (15 cases of pancreatic ductal adenocarcinoma and 13 cases of other diseases) were examined. Formalin-fixed, paraffin-embedded tissue sections were examined for proliferating cell activity using histone H3 mRNA in situ hybridization and immunostaining for Ki-67. In the normal pancreas, the labelling indices for proliferating cells were low and no generating zone was found. The following progressive increase was found in the labelling indices: normal ductal epithelium < mucinous metaplasia without papillary hyperplasia < mucinous metaplasia with papillary hyperplasia < ductal carcinoma. In the pancreatic ductal adenocarcinomas, the S-phase fraction, as defined by the ratio H3-mRNA-labelling index/Ki-67-labelling index, increased as the degree of differentiation decreased. Mucinous metaplasia with papillary hyperplasia showed organoid differentiation toward pyloric mucosa. If used in combination with other proliferative markers on paraffin-embedded tissue sections, histone H3 mRNA in situ hybridization could open broader perspectives on the biology of cell proliferation in the pancreatic ductal system.