The activity of thymidine phosphorylase (dThdPase) has been reported t
o increase in several types of malignant tumors. Experimental evidence
has shown that dThdPase is identical to platelet-derived endothelial
cell growth factor, and that dThdPase has angiogenic activity. We exam
ined the expression of dThdPase to investigate whether the expression
of dThdPase correlates with angiogenesis, clinicopathologic features a
nd the prognosis of patients with human gastric carcinomas. Microvesse
ls were assessed by immunostaining endothelial cells for factor VIII.
We counted microvessels in the tumors of 158 patients whose tumors wer
e completely removed surgically. Microvessels were counted in a X 400
field in the most active areas of neovascularization. We purified a mo
noclonal antibody (TMA-1) against dThdPase and studied the expression
of dThdPase using TMA-1 in the same serial sections as those used for
the detection of factor VIII. The correlation between angiogenesis and
dThdPase, and the clinicopathological significance of dThdPase, in pa
tients with gastric carcinoma were examined. The positive expression o
f dThdPase was more frequent (P < 0.001) in gastric carcinomas (67/158
, 43.4%) than that in normal tissues (12/158, 7.6%). The average micro
vessel count in dThdPase-positive gastric carcinomas was higher (P < 0
.001) than that in dThdPase negative carcinomas. The percentage of gas
tric carcinoma cells expressing dThdPase was significantly correlated
with the microvessel count (P < 0.001). Further, the average size of d
ThdPase-positive carcinomas was significantly larger (P < 0.001) than
that of negative carcinomas and the mean microvessel count in dThdPase
-positive gastric carcinomas was also significantly higher (P < 0.001)
than that in dThdPase-negative carcinomas. There was a significant co
rrelation between the positive expression of dThdPase and microvessel
count (P < 0.001) or lymph node metastasis (P = 0.013) by multivariate
logistic analysis. Further, patients with dThdPase-positive carcinoma
showed a significantly worse prognosis than those with dThdPase-negat
ive carcinoma overall and in stage III. These findings indicate that t
he expression of dThdPase in gastric carcinomas is related to progress
ion and metastasis, and this enzyme affects the prognosis of some pati
ents with the disease.