Correlation between serum tryptase, mast cells positive to tryptase and microvascular density in colo-rectal cancer patients: possible biological-clinical significance

PLoS One. 2014 Jun 10;9(6):e99512. doi: 10.1371/journal.pone.0099512. eCollection 2014.

Abstract

Background: Tryptase is a serin protease stored and released from mast cells (MCs) that plays a role in tumour angiogenesis. In this study we aimed to evaluate serum tryptase levels in colo-rectal cancer (CRC) patients before (STLBS) and after (STLAS) radical surgical resection. We also evaluated mast cell density positive to tryptase (MCDPT) and microvascular density (MVD) in primary tumour tissue.

Methods: A series of 61 patients with stage B and C CRC (according to the Astler and Coller staging system) were selected. Serum blood samples were collected from patients one day before and one day after surgery. Tryptase levels were measured using the UniCAP Tryptase Fluoroenzymeimmunoassay (Pharmacia, Uppsala, Sweden). Tumour sections were immunostained with a primary anti-tryptase antibody (clone AA1; Dako, Glostrup, Denmark) and an anti CD-34 antibody (QB-END 10; Bio-Optica Milan, Italy) by means of immunohistochemistry and then evaluated by image analysis methods.

Results: The mean ± s.d. STLBS and STLAS was 5.63±2.61 µg/L, and 3.39±1.47 µg/L respectively and a significant difference between mean levels was found: p = 0.000 by t-test. The mean ± s.d. of MCDPT and MVD was 8.13±3.28 and 29.16±7.39 respectively. A strong correlation between STLBS and MVD (r = 0.83, p = 0.000); STLBS and MCDPT (r = 0.60, p = 0.003); and MCDPT and MVD (r = 0.73; p = 0.001) was found.

Conclusion: Results demonstrated higher STLBS in CRC patients, indicating an involvement of MC tryptase in CRC angiogenesis. Data also indicated lower STLAS, suggesting the release of tryptase from tumour-infiltrating MCs. Serum tryptase levels may therefore play a role as a novel bio-marker predictive of response to radical surgery. In this context tryptase inhibitors such as Gabexate and Nafamostat Mesilate might be evaluated in adjuvant clinical trials as a new anti-angiogenic approach.

MeSH terms

  • Colorectal Neoplasms / blood supply
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / surgery
  • Female
  • Humans
  • Intestinal Mucosa / pathology
  • Male
  • Mast Cells / enzymology*
  • Mast Cells / pathology
  • Microvessels / pathology*
  • Tryptases / blood*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Vascular Endothelial Growth Factor A
  • Tryptases

Grants and funding

The authors have no support or funding to report.