Cancerous, but not stromal, thrombospondin-2 contributes prognosis in pulmonary adenocarcinoma.
Thrombospondin (TSP)-2 is known to be an endogenous negative regulator of vascularization in human cancer. However, it is unclear whether TSP-2 expression is related to neovascularization and prognosis in non-small cell lung cancer. In this study, we quantitatively examined the expression of TSP-2 mRNA by real-time reverse transcription-polymerase chain reaction (RT-PCR) in 102 pulmonary adenocarcinomas. All 102 carcinoma specimens expressed TSP-2 mRNA. The expression of TSP-2 mRNA in carcinoma was significantly higher than normal lung tissues (p<0.0001, Kruskal-Wallis test). Sizes of tumors were significantly correlated with TSP-2 gene expression (p=0.0179, Kruskal-Wallis test). The TSP-2 expression levels of the stage II/III pulmonary carcinomas were significantly increased as compared to those of stage I (p=0.0136, Kruskal-Wallis test). Thirty-five patients with high TSP-2 mRNA expression showed poor prognosis in survival (p=0.0139, log-rank test). We examined TSP-2 protein localizations in the pulmonary adenocarcinoma overexpressing TSP-2 mRNA. The TSP-2 localizations were categorized in two patterns: cancerous TSP-2 expression pattern (TSP-2 expression in the cancerous cells) and non-cancerous TSP-2 expression pattern (TSP-2 expression in the stromal lymphoid cells). Pulmonary adenocarcinoma patients with cancerous TSP-2 expression pattern showed good prognosis (p=0.0322; Fisher's probability exact test). Pulmonary adenocarcinoma patients with non-cancerous TSP-2 expression pattern showed poor prognosis (p=0.0220; Fisher's probability exact test). Non-cancerous TSP-2 expressions may reflect secondary reactions in the cancerous stroma. The stromal TSP-2 expression is not enough to suppress growth of pulmonary adenocarcinoma, while the cancerous TSP-2 expression directly inhibits growth of the carcinoma.
Chijiwa
Tsuyoshi
T
Department of Pathology, Tokai University School of Medicine, Kanagawa 259-1193, Japan.
Abe
Yoshiyuki
Y
Inoue
Yoshimasa
Y
Matsumoto
Hozumi
H
Kawai
Kenji
K
Matsuyama
Masahiro
M
Miyazaki
Noriyuki
N
Inoue
Hiroshi
H
Mukai
Masaya
M
Ueyama
Yoshito
Y
Nakamura
Masato
M
D000230:Adenocarcinoma / Q000098:blood supply / Q000737:chemistry / Q000401:mortality*; D000368:Aged; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D017154:Stromal Cells / Q000737:chemistry; D019699:Thrombospondins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D000099262:Thrombospondin 2
D012333:RNA, Messenger; D019699:Thrombospondins; D000099262:Thrombospondin 2