Expression of thymidylate synthase is correlated with proliferative activity in non-small cell lung cancer (NSCLC)

Many experimental studies have revealed that enhanced thymidylate synthase (TS) expression is significantly correlated with higher proliferative activity of tumor cells, which may account for a poor prognosis of high-TS patients. However, only a few clinical studies have focused on the correlation between TS status and cell proliferation. Therefore, we assessed the correlation between TS expression and proliferative index (PI) as a marker of cell proliferation or p53 status in a total of 109 patients with completely resected pathologic stage I, non-small cell lung cancer (NSCLC). PI was defined as the percentage of tumor cells with positive staining against proliferative cell nuclear antigen (PCNA). The mean PIs of TS-high and TS-low tumors were 48.2% and 34.4% respectively, showing a significantly higher proliferative activity of TS-high tumor (P=0.020); when stratified according to histological type, the difference was significant in adenocarcinoma (P=0.038), but not in squamous cell carcinoma. There was no significant correlation between TS expression and p53 status. In conclusion, tumor cells with higher TS expression have higher proliferative activity in NSCLC, especially in adenocarcinoma.