Significance of thymidylate synthase and thyroid transcription factor 1 expression in patients with nonsquamous non-small cell lung cancer treated with pemetrexed-based chemotherapy.

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7579 Background: To evaluate whether thymidylate synthase (TS) or thyroid transcription factor 1 (TTF1) protein expression can predict clinical outcome for pemetrexed-based chemotherapy in patients with nonsquamous non-small cell lung cancer (NSCLC). Methods: Two hundred eighty-five consecutive patients with nonsquamous NSCLC treated with pemetrexed-based chemotherapy were immunohistochemically analyzed for the expression of TS and TTF1. Results: TS and TTF1 expression were successfully analyzed in 193 and 284 cases, respectively. Tumors with TS-negativity or TTF1-positivity was more frequent in groups of female, younger age, adenocarcinoma, or never-smoker. Higher response rates for pemetrexed-based chemotherapy were associated with TS-negativity (33.7% vs. 14.1%, P = 0.002) and TTF1-positivity (28.1% vs. 9.8%, P < 0.001), respectively. In univariate analysis, progression-free survival (PFS) for pemetrexed-based chemotherapy was significantly longer in groups of adenocarcinoma (2.9 vs. 1.4 months, P = 0.001), TS-negativity (4.1 vs 2.0 months, P = 0.001), and TTF1-positivity (3.9 vs. 1.3 months, P < 0.001). In multivariate analysis, TS-negativity (HR = 0.69; 95% CI, 0.50–0.96) and TTF1-positivity (HR = 0.51; 95% CI, 0.35–0.73) were associated with longer PFS, respectively. Patients with TTF1-positive tumors also had significantly longer overall survival time than patients with TTF1-negative tumors (25.4 vs. 14.2 months, HR = 0.55; 95% CI, 0.39–0.77). Conclusions: Low TS or high TTF1 protein expression was significantly associated with better clinical outcomes in nonsquamous NSCLC patients who were treated with pemetrexed-based chemotherapy. The predictive role of TS or TTF1 expression is required to be further validated in a prospective randomized study.