Expression of thrombospondin-1 in pancreatic carcinoma: correlation with microvessel density.
Thrombospondin-1 (TSP-1) is a multifunctional platelet and extracellular matrix protein that is involved in angiogenesis. Under certain pathological conditions, 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 density (MVD), a representation of the overall degree of angiogenesis in carcinomas. Northern blot analysis for TSP-1 mRNA was performed in seven additional cases. Eighty-seven tumors showed strong TSP-1 immunoreactivity, nine carcinomas were only weakly positive, and two lesions were negative for TSP-1. TSP-1 immunoreactivity was detected in the extracellular matrix, mostly at the invasion front of the tumor. Using Northern blot analysis, we observed high levels of TSP-1 mRNA in three out of seven pancreatic carcinomas. The mean MVD in pancreatic carcinoma was 38.8 vessels per mm2. Tumors with a high expression of TSP-1 showed a higher MVD and the correlation between TSP-1 immunoreactivity and microvessel density was highly significant (P=0.003). As a modulator of angiogenesis, TSP-1 is strongly expressed in most pancreatic adenocarcinomas and is likely to contribute to the extensive neovascularization and spread of this highly aggressive tumor.
Kasper
H U
HU
Department of Pathology, Otto-von-Guericke University, Magdeburg, Germany. hukasper@hotmail.com
Ebert
M
M
Malfertheiner
P
P
Roessner
A
A
Kirkpatrick
C J
CJ
Wolf
H K
HK
D000230:Adenocarcinoma / Q000098:blood supply* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D015152:Blotting, Northern; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D019700:Thrombospondin 1