title: Vascular proliferation is associated with survival in pancreatic ductal adenocarcinoma.
abstract: In pancreatic ductal adenocarcinoma (PDAC), the benefit of current chemotherapy and radiation therapy is very limited, even in radically resected patients. New treatment strategies, for example based on the inhibition of the tumour's blood supply, need to be explored. We have investigated angiogenesis markers and their associations with relapse and survival in 52 histologically confirmed cases of PDAC. Angiogenesis in the primary tumour was evaluated by microvessel density (MVD), vascular proliferation index (VPI) and the presence of glomeruloid microvascular proliferations (GMP). These features were analysed in the context of clinicopathological variables, KRAS mutation status, relapse location and survival. MVD (median 134 microvessels/mm(2) , range 88-177) and VPI (median 3.2%, range 1.6-4.9) were associated with larger tumour size and lymph node metastasis. MVD was also related to the occurrence of liver metastases. Both variables were associated with survival in univariate and multivariate analyses. GMPs were present in 32 (62%) of the cases. Patients who exhibited MVD and VPI values above median, and GMP positivity, had a median survival of only 4.2 months after surgery. In conclusion, the angiogenesis markers MVD and VPI have a significant impact on survival. By also including GMP, a subgroup of PDAC patients with particularly short survival could be identified.
authors.affiliation: Department of Gastrointestinal Surgery, Haukeland University Hospital, Bergen, Norway.
authors.forename: Dag
authors.initials: D
authors.lastname: Hoem
authors.forename: Oddbjørn
authors.initials: O
authors.lastname: Straume
authors.forename: Heike
authors.initials: H
authors.lastname: Immervoll
authors.forename: Lars A
authors.initials: LA
authors.lastname: Akslen
authors.forename: Anders
authors.initials: A
authors.lastname: Molven
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000098:blood supply* / Q000401:mortality; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009389:Neovascularization, Pathologic / Q000401:mortality*; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000401:mortality; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: Angiogenesis; GMP; KRAS mutation; MVD; VPI; pancreatic cancer; survival