Transforming growth factor-β1 and α-smooth muscle actin in stromal fibroblasts are associated with a poor prognosis in patients with clinical stage I-IIIA nonsmall cell lung cancer after curative resection

The aims of this study were to investigate the expression of transforming growth factor-beta 1 (TGF-beta 1) and alpha-smooth muscle actin (alpha-SMA) in surgical resection specimens from nonsmall cell lung cancer (NSCLC) and to evaluate the prognostic significance of this gene expression in stromal fibroblasts for patients with clinical stage I-IIIA NSCLC. The immunohistochemical expression of TGF-beta 1 and alpha-SMA was evaluated in 78 formalin-fixed paraffin-embedded tumor specimens from clinical stage I-IIIA NSCLC. Correlations between this gene expression and the clinicopathologic characteristics were determined by chi-square test. The prognostic impact of this gene expression in stromal fibroblasts with regard to overall survival (OS) was determined by Kaplan-Meier and Cox hazard proportional model. The percentages of high TGF-beta 1 expression in stromal fibroblasts and cancer cells were 19.2 % (15/78) and 35.9 % (28/78), respectively. There were 28.2 % (22/78) of patients with high alpha-SMA expression in stromal fibroblasts. The analysis revealed a significant positive association between TGF-beta 1 expression in stromal fibroblasts and in cancer cells (chi (2) = 4.86, p = 0.03). No significant association was found between TGF-beta 1 in cancer cells and alpha-SMA expression in stromal fibroblasts (chi (2) = 0.978, p = 0.326). The 3-year OS rates with low and high TGF-beta 1 expression in stromal fibroblasts were 52.4 and 26.7 %, respectively (chi (2) = 5.42, p = 0.019). The 3-year OS rates with low and high alpha-SMA expression in stromal fibroblasts were 53.9 and 31.0 %, respectively (chi (2) = 5.01, p = 0.025). The multivariate analysis revealed that clinical stage and TGF-beta 1 and alpha-SMA expression levels in stromal fibroblasts were identified as independent predictive factors of OS. The results suggest that the expression level of TGF-beta 1 and alpha-SMA in stromal fibroblasts may have prognostic significance in patients with clinical stage I-IIIA NSCLC after curative resection.