Inflammatory cells contribute to the generation of an angiogenic phenotype in pancreatic ductal adenocarcinoma - PubMed (original) (raw)

Inflammatory cells contribute to the generation of an angiogenic phenotype in pancreatic ductal adenocarcinoma

I Esposito et al. J Clin Pathol. 2004 Jun.

Abstract

Background: Inflammatory cells contribute to the growth and spread of human malignancies by producing molecules that enhance tumour invasiveness.

Aims: To characterise the inflammatory infiltrate in pancreatic ductal adenocarcinoma and to analyse its contribution to angiogenesis and its prognostic relevance.

Methods: Immunohistochemistry was used to identify inflammatory cells and evaluate the expression of proangiogenic and prolymphangiogenic molecules (vascular endothelial growth factor A (VEGF-A), VEGF-C, and basic fibroblast growth factor (bFGF)) by inflammatory and cancer cells in 137 pancreatic cancers. Intratumorous microvessel density (IMD) was assessed using CD34 as an endothelial cell marker.

Results: There were significantly more mast cells and macrophages in pancreatic cancers than in normal pancreas and the number of mast cells directly correlated with the presence of lymph node metastases. However, there was no relation between numbers of infiltrating inflammatory cells and the presence of chronic pancreatitis (CP)-like changes in the parenchyma surrounding the tumour. Double immunostaining revealed that both pancreatic mast cells and macrophages express VEGF-A, VEGF-C, and bFGF. These factors were also expressed in the tumour cells in many cases. The numbers of VEGF-A expressing tumour cells and bFGF expressing tumour and inflammatory cells significantly correlated with IMD. Moreover, tumours with higher IMD had higher numbers of infiltrating mast cells and macrophages.

Conclusions: Mononuclear inflammatory cells of the non-specific immune response are recruited to pancreatic cancer tissues independent of the presence of CP-like changes, may influence the metastatic capacity of the cancer cells, and may contribute to the development of tumours with high angiogenic activity.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Expression of proangiogenic growth factors in pancreatic ductal adenocarcinoma. Strong immunoreactivity for (A) vascular endothelial growth factor A (VEGF-A), (B) VEGF-C, and (C) basic fibroblast growth factor in the cytoplasm of the tumour cells; positive inflammatory cells are visible in the stroma around the tumour cells and (D) at the tumour periphery.

Figure 2

Figure 2

Characterisation of the inflammatory infiltrate in pancreatic ductal adenocarcinoma. (A) Tryptase positive mast cells and (B) CD68 positive macrophages are the most common inflammatory cells in the stroma of pancreatic ductal adenocarcinoma. Double immunohistochemistry shows that (C) mast cells and (D) macrophages (red staining) are a source of vascular endothelial growth factor C (brown staining) in pancreatic ductal adenocarcinoma. The arrowheads point to double positive inflammatory cells, the arrows to single (brown) stained inflammatory cells.

Figure 3

Figure 3

Survival analysis. (A) The survival of patients whose tumours exhibited a high number of infiltrating mast cells and a high ntratumorous microvessel density (IMD; solid line) was shorter than that of patients whose tumours exhibited a low number of infiltrating mast cells and a low IMD (broken line). However, the difference was not significant. (B) The same tendency was seen when the number of infiltrating macrophages was combined with the IMD (solid line, high number of macrophages and high IMD; broken line, low number of macrophages and low IMD). Crosses indicate censored cases.

Similar articles

Cited by

References

    1. Solcia E, Capella G, Klöppel G. Tumors of the exocrine pancreas. In: Rosai J, Sobin L, eds. Atlas of tumor pathology. Tumors of the pancreas. Washington DC: Armed Forces Institute of Pathology, 1997:64–88.
    1. Ryu B, Jones J, Hollingsworth MA, et al. Invasion-specific genes in malignancy: serial analysis of gene expression comparisons of primary and passaged cancers. Cancer Res 2001;61:1833–8. - PubMed
    1. Iacobuzio-Donahue CA, Ryu B, Hruban RH, et al. Exploring the host desmoplastic response to pancreatic carcinoma: gene expression of stromal and neoplastic cells at the site of primary invasion. Am J Pathol 2002;160:91–9. - PMC - PubMed
    1. Gouon-Evans V, Lin EY, Pollard JW. Requirement of macrophages and eosinophils and their cytokines/chemokines for mammary gland development. Breast Cancer Res 2002;4:155–64. - PMC - PubMed
    1. Wong YC, Wang YZ. Growth factors and epithelial–stromal interactions in prostate cancer development. Int Rev Cytol 2000;199:65–116. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources