Medical oncology, Cancérologie, Pharmacology drugs, Pharmacologie, galénique, Sciences biologiques et medicales, Biological and medical sciences, Sciences medicales, Medical sciences, Pharmacologie. Traitements medicamenteux, Pharmacology. Drug treatments, Anticancéreux, Antineoplastic agents, Tumeurs, Tumors, Tumeurs multiples. Tumeurs solides. Tumeurs chez l'enfant (généralités), Multiple tumors. Solid tumors. Tumors in childhood (general aspects), Gastroenterologie. Foie. Pancreas. Abdomen, Gastroenterology. Liver. Pancreas. Abdomen, Foie. Voies biliaires. Circulation portale. Pancréas exocrine, Liver. Biliary tract. Portal circulation. Exocrine pancreas, Cancer, Cáncer, Pathologie de l'appareil digestif, Digestive diseases, Aparato digestivo patología, Pathologie du pancréas, Pancreatic disease, Páncreas patología, Tumeur maligne, Malignant tumor, Tumor maligno, Cancer du pancréas, Pancreas cancer, Cáncer del páncreas, Expression génique, Gene expression, Expresión genética, Glycane, Glycan, Glicano, Mucine, Mucin, Mucina, Protéine, Protein, and Proteína
Purpose: Mucin expression is a common feature of most adenocarcinomas and features prominently in current attempts to improve diagnosis and therapy for pancreatic cancer and other adenocarcinomas. We investigated the expression of a number of mucin core proteins and associated O-linked glycans expressed in pancreatic adenocarcinoma—sialyl Tn (STn), Tn, T antigen, sialyl Lewis A (CA19-9), sialyl Lewis C (SLeC), Lewis X (LeX), and sialyl LeX (SLeX)—during the progression of pancreatic cancer from early stages to metastatic disease. Experimental Design: Immunohistochemical analyses of mucin and associated glycan expression on primary tumor and liver metastatic tumor samples were conducted with matched sets of tissues from 40 autopsy patients diagnosed with pancreatic adenocarcinoma, 14 surgically resected tissue samples, and 8 normal pancreata. Results: There were significant changes in mucin expression patterns throughout disease progression. MUC1 and MUC4 were differentially glycosylated as the disease progressed from early pancreatic intra-epithelial neoplasias to metastatic disease. De novo expression of several mucins correlated with increased metastasis indicating a potentially more invasive phenotype, and we show the expression of MUC6 in acinar cells undergoing acinar to ductal metaplasia. A cancer field-effect that included changes in mucin protein expression and glycosylation in the adjacent normal pancreas was also seen. Conclusions: There are significant alterations in mucin expression and posttranslational processing during progression of pancreatic cancer from early lesions to metastasis. The results are presented in the context of how mucins influence the biology of tumor cells and their microenvironment during progression of pancreatic cancer.