Thymidine phosphorylase expression in gallbladder adenocarcinomas.
Giatromanolaki A., Sivridis E., Simopoulos C., Polychronidis A., Gatter KC., Harris AL., Koukourakis MI.
The expression of thymidine phosphorylase (TP), a potent chemotactic factor for endothelial cells, was studied in 60 adenocarcinomas of the gallbladder, by use of immunohistochemical techniques. Results on patterns of TP expression were correlated with angiogenesis (anti-CD31), histopathological variables, and patient survival. TP was frequently expressed in tumor cells, stromal cells, tumor-associated macrophages, and lymphocytes of gallbladder adenocarcinomas. The expression was mixed nuclear/cytoplasmic. However, only nuclear TP (TPnuc) expression by tumor cells was correlated with increased angiogenic activity. High angiogenesis, assessed as microvessel density (MVD), was the most significant prognostic factor. The subgroup of patients with TPnuc and medium/high MVD had the worst prognosis as evaluated by the survival curves. Furthermore, CD31+ lymphocytes, frequently seen in carcinomas with high-fibroblastic TP reactivity, were connected with an improved survival. It is concluded that angiogenesis, as verified by multivariate analysis, is the most important prognostic factor in gallbladder carcinomas. In these tumors, high histologic grade and low CD31+ lymphocytic infiltration are also independent predictors of poor prognosis. TP is associated with an aggressive phenotype apparently because of its anglogenic activity. Therapeutic strategies targeting TP may be of value in patients overexpressing this enzyme.