Histopathological tumor invasion of the mesenterico-portal vein is characterized by aggressive biology and stromal fibroblast activation

HPB (Oxford). 2017 Jan;19(1):67-74. doi: 10.1016/j.hpb.2016.10.002. Epub 2016 Nov 5.

Abstract

Background: Mesenterico-portal vein resection (PVR) during pancreatoduodenectomy for pancreatic head cancer was established in the 1990s and can be considered a routine procedure in specialized centers today. True histopathologic portal vein invasion is predictive of poor prognosis. The aim of this study was to examine the relationship between mesenterico-portal venous tumor infiltration (PVI) and features of aggressive tumor biology.

Methods: Patients receiving PVR for pancreatic ductal adenocarcinoma of the pancreatic head were identified from a prospectively maintained database. Immunohistochemical staining of tumor tissue was performed for the markers of epithelial-mesenchymal transition (EMT) E-Cadherin, Vimentin and beta-Catenin. Morphology of cancer-associated fibroblasts (CAFs) was assessed as inactive or activated. Statistical calculations were performed with MedCalc software.

Results: In total, 41 patients could be included. Median overall survival was 25 months. PVI was found in 17 patients (41%) and was significantly associated with loss of membranous E-Cadherin in tumor buds (p = 0.020), increased Vimentin expression (p = 0.03), activated CAF morphology (p = 0.046) and margin positive resection (p = 0.005).

Conclusion: Our findings suggest that PVI is associated with aggressive tumor biology and disseminated growth less amenable to margin-negative resection.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD
  • Biomarkers, Tumor / analysis
  • Cadherins / analysis
  • Carcinoma, Pancreatic Ductal / chemistry
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / pathology*
  • Carcinoma, Pancreatic Ductal / surgery
  • Databases, Factual
  • Epithelial-Mesenchymal Transition
  • Female
  • Fibroblasts / chemistry
  • Fibroblasts / pathology*
  • Humans
  • Male
  • Mesenteric Veins / chemistry
  • Mesenteric Veins / pathology*
  • Mesenteric Veins / surgery
  • Middle Aged
  • Neoplasm Invasiveness
  • Pancreatic Neoplasms / chemistry
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / surgery
  • Pancreaticoduodenectomy
  • Portal Vein / chemistry
  • Portal Vein / pathology*
  • Portal Vein / surgery
  • Stromal Cells / chemistry
  • Stromal Cells / pathology*
  • Time Factors
  • Treatment Outcome
  • Tumor Microenvironment
  • Vimentin / analysis
  • beta Catenin / analysis

Substances

  • Antigens, CD
  • Biomarkers, Tumor
  • CDH1 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • Vimentin
  • beta Catenin