Vascular proliferation is associated with survival in pancreatic ductal adenocarcinoma

APMIS. 2013 Nov;121(11):1037-46. doi: 10.1111/apm.12057. Epub 2013 Mar 13.

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.

Keywords: Angiogenesis; GMP; KRAS mutation; MVD; VPI; pancreatic cancer; survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood supply*
  • Adenocarcinoma / mortality
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Pancreatic Ductal / blood supply*
  • Carcinoma, Pancreatic Ductal / mortality
  • Cell Proliferation
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Neovascularization, Pathologic / mortality*
  • Pancreatic Neoplasms / blood supply*
  • Pancreatic Neoplasms / mortality
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins / genetics

Substances

  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins