Thrombospondin-1 expression and clinical implications in malignant pleural mesothelioma.
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 surrounding normal lung samples. In MPM tumors, vascular endothelial growth factor (VEGF) expression also was examined. Differences between different valuables were analyzed using the Mann-Whitney U test. Survival curves were obtained by the Kaplan-Meier method and the survival rate was assessed by the log 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) and 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 significantly greater in high VEGF-expressing tumors (2.63 +/- 0.51) compared with low VEGF-expressing tumors (1.17 +/- 0.39; P < 0.0001) and TSP-1 expression 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 in patients with low VEGF-expressing tumors, TSP-1 itself appeared to have no overall impact on survival. The methylation status of a CpG island associated 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 between TSP-1 and VEGF in MPM merit further investigation for possible innovative therapeutic interventions.
Ohta
Y
Y
Aerodigestive Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.
Shridhar
V
V
Kalemkerian
G P
GP
Bright
R K
RK
Watanabe
Y
Y
Pass
H I
HI
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000032:analysis*; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000096:biosynthesis; D008297:Male; D008654:Mesothelioma / Q000473:pathology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic; D010997:Pleural Neoplasms / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D019700:Thrombospondin 1 / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D014408:Biomarkers, Tumor; D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors