Thrombospondin-1 expression and clinical implications in malignant pleuralmesothelioma

BACKGROUND. The role of thrombospondin-1 (TSP-1) in tumor angiogenesis and progression is controversial. The authors assessed the impact of TSP-1 as a prognostic indicator in malignant pleural mesothelioma (MPM). METHODS. TSP-1 expression was assessed by reverse transcriptase-polymerase chain reaction using 5 normal pleural samples, 78 MPM tumors, and 43 surrou nding normal lung samples. In MPM tumors, vascular endothelial growth facto r (VEGF) expression also was examined. Differences between different valuab les were analyzed using the Mann-Whitney U test. Survival curves were obtai ned by the Kaplan-Meier method and the survival rate was assessed by the lo g rank test. RESULTS. TSP-1 was highly expressed in 74 of the 78 MPM tumors (95%) with a mean value of 2.27 +/- 0.42 compared with normal pleura (0.50 +/- 0.06) an d surrounding normal lung (0.96 +/- 0.20) (P = 0.05 vs. normal pleura and P = 0.0006 vs. surrounding normal lung). The mean TSP-1 expression was signi ficantly greater in high VEGF-expressing tumors (2.63 +/- 0.51) compared wi th low VEGF-expressing tumors (1.17 +/- 0.39; P < 0.0001) and TSP-1 express ion was lower in patients with TNM Stage III/IV disease (n = 60) (1.85 +/- 0.37) than in patients with Stage I/II disease (n = 13) (4.46 +/- 1.74) (P = 0.025). The TSP-1 expression levels in tumors with lymph node metastases were significantly lower than in those without lymph node metastases (P = 0 .0305). Although high TSP-1 expression was associated with good prognosis i n patients with low VEGF-expressing tumors, TSP-1 itself appeared to have n o overall impact on survival. The methylation status of a CpG island associ ated with the TSP-1 promoter was evident in MPM tumor samples despite high levels of TSP-1 mRNA expression. CONCLUSIONS. TSP-1 is overexpressed in MPM tumors but its expression is of little value as a prognostic indicator in MPM. However, the relations betwe en TSP-1 and VEGF in MPM merit further investigation for possible innovativ e therapeutic interventions. Cancer 1999;85:2570-6. (C) 1999 American Cance r Society.