Heterogeneic distribution of thymidine phosphorylase between primary tumors and metastatic lesions of human pancreatic ductal carcinoma: implicationsfor the efficacy of chemotherapy with 5-FU or its derivatives

Purpose. It has been suggested that the expression of thymidine phosphoryla se (TdRPase) correlates with the malignant potential of various cancers, bu t its involvement in human invasive ductal carcinoma (IDC) of the pancreas has not been reported. In the present study, the distribution and clinical significance of TdRPase in IDCs and benign diseases of the pancreas were as sessed, especially in relation to the efficacy of chemotherapy with 5-FU or its derivatives. Method: The expression of TdRPase in 148 specimens of pan creatic IDCs (66 primary lesions, 46 nodal lesions and 36 distant metastase s from 126 patients) and in 24 specimens of benign diseases (4 cystadenomas , 3 hyperplasias, and 17 chronic pancreatitises) was examined by immunohist ochemical staining with anti-TdRPase monoclonal antibody and evaluated in t erms of three grades of immunoreactivity: negative 0, low 1, or high 2. Res ults. Positive TdRPase staining (low and high immunoreactivity) was detecte d in 71% (47/66) of the primary lesions, in 46% (21/46) of the involved nod es, in 53% (19/36) of various lesions of distant metastasis, and in 37% (9/ 24) of the benign diseases. The staining intensity was significantly higher in the IDC tissues than in the benign disease tissues, and significantly l ower in the metastatic lesions than in the primary lesions. TdRPase reactiv ity did not correlate with the survival rate in both resectable and unresec table IDCs. In patients with both primary tumor and nodal involvement, howe ver, high TdRPase activity in involved nodes was significantly associated w ith a poor prognosis. On the other hand, although adjuvant chemotherapy was found to improve the survival of patients, TdRPase activity in the tumor d id not show any significant relationship with the efficacy of chemotherapy with 5-FU or its derivatives. Conclusions: The present study suggested that in pancreatic IDC the activity of TdRPase in primary lesions is different from that in metastatic lesions, and that DNA is synthesized mainly through the salvage pathway in primary lesions and through a de novo pathway in me tastatic lesions. This may be one of the reasons for the heterogeneity in c hemosensitivity of human pancreatic IDC.