Expression of thrombospondin-1 in pancreatic carcinoma: correlation with microvessel density

Thrombospondin-1 (TSP-1) is a multifunctional platelet and extracellular ma trix protein that is involved in angiogenesis. Under certain pathological c onditions, e.g., malignant tumors, high concentrations of TSP-1 work as an angiogenic agonist. Here we examined 98 pancreatic carcinomas with respect to TSP-1 immunoreactivity and its correlation to intratumoral microvessel d ensity (MVD), a representation of the overall degree of angiogenesis in car cinomas. Northern blot analysis for TSP-1 mRNA was performed in seven addit ional cases. Eighty-seven tumors showed strong TSP-1 immunoreactivity, nine carcinomas were only weakly positive, and two lesions were negative for TS P-1. TSP-1 immunoreactivity was detected in the extracellular matrix, mostl y at the invasion front of the tumor. Using Northern blot analysis, we obse rved high levels of TSP-1 mRNA in three out of seven pancreatic carcinomas. The mean MVD in pancreatic carcinoma was 38.8 vessels per mm(2). Tumors wi th a high expression of TSP-1 showed a higher MVD and the correlation betwe en TSP-1 immunoreactivity and microvessel density was highly significant (P =0.003). As a modulator of angiogenesis, TSP-1 is strongly expressed in mos t pancreatic adenocarcinomas and is likely to contribute to the extensive n eovascularization and spread of this highly aggressive tumor.