Impact of thymidylate synthase protein expression on efficacy of chemotherapy in advanced lung cancer patients.

Advanced lung cancer is primarily treated with platinum combination chemotherapy, however, its prognosis remains poor. The aim of this study was to examine the correlation between the expression of thymidylate synthase (TS) in cancer tissues and the efficacy of chemotherapy in patients with advanced lung cancer in order to clarify the role of TS in the overall response. In total, 120 patients diagnosed with lung cancer between June 2004 and December 2010 at Nihon University Hospital, Tokyo, Japan, were included in this study. Cancer tissue specimens were obtained from the included patients by surgery or bronchofiberscopy prior to treatment. The expression of TS protein was evaluated using specimens immunostained with anti-TS antibody and H-scoring. TS protein expression tended to be higher in smokers compared with non-smokers. Overall survival (OS) (median value) was significantly prolonged in the low TS expression group compared with the high TS expression group. More favorable therapeutic effects were observed in the high TS expression group compared with the low TS expression group, when carboplatin + paclitaxel combined chemotherapy (CbPac therapy) was used. When the therapeutic effects were compared between CbPac therapy and carboplatin + pemetrexed combined chemotherapy (CbPem therapy) in the high TS expression group, prolongation of OS (median value) was observed with CbPac therapy. The present study suggests that TS protein expression is a critical factor in determining the efficacy of CbPac therapy in lung cancer. CbPac therapy is more effective when TS protein is highly expressed in lung cancer tissue.