title: Lymphatic vessel density and vascular endothelial growth factor-C expression correlate with malignant behavior in human pancreatic endocrine tumors.
abstract: Metastatic dissemination of tumor cells to regional lymph nodes is a common early feature of many human cancers including pancreatic adenocarcinoma. In contrast, lymph node metastasis is more variably observed in pancreatic endocrine tumors. The objective of this study was to assess the lymphatic system of human pancreatic endocrine tumors and correlate this to clinical behavior. Immunohistochemistry was performed using antibodies to two recently identified markers of lymphatic endothelium, namely, LYVE-1 and podoplanin, and to the lymphangiogenic factor vascular endothelial growth factor (VEGF)-C. As has been reported previously, we observed that in the normal pancreas, islets of Langerhans are devoid of intra-islet lymphatics, but that lymphatics are present in connective tissue in association with ducts and blood vessels. We found that both benign and malignant pancreatic endocrine tumors contain intratumoral lymphatic vessels. Lymphatic vessel density was related to the size of the tumor in benign tumors and to the presence of liver metastasis but not to lymph node metastasis in malignant tumors. VEGF-C was expressed in tumor cells: 4 of 19 (21%) benign tumors were positive, whereas 6 of 9 (67%) borderline tumors and 9 of 11 (82%) carcinomas were positive. These findings strongly suggest that lymphangiogenesis occurs in pancreatic endocrine tumors and that lymphatic invasion and the development of metastases are associated with VEGF-C expression.
authors.affiliation: Services of Clinical Pathology, Gastroenterology and Hepatology, and Digestive Surgery, Geneva University Hospital, Geneva, Switzerland. laura.rubbia-brandt@hcuge.ch
authors.forename: Laura
authors.initials: L
authors.lastname: Rubbia-Brandt
authors.forename: Benoit
authors.initials: B
authors.lastname: Terris
authors.forename: Emile
authors.initials: E
authors.lastname: Giostra
authors.forename: Bertrand
authors.initials: B
authors.lastname: Dousset
authors.forename: Philippe
authors.initials: P
authors.lastname: Morel
authors.forename: Michael S
authors.initials: MS
authors.lastname: Pepper
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010182:Pancreatic Diseases / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000473:pathology*; D020799:Pancrelipase / Q000502:physiology; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis*
chemical_list: C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C; D020799:Pancrelipase