Thrombospondin-1 and -2 messenger RNA expression in normal and neoplastic endometrial tissues: correlation with angiogenesis and prognosis.
The role of thrombospondin (TSP) in tumor angiogenesis and progression remains controversial. The expression of TSP-1 and TSP-2 mRNAs was assessed. Furthermore, TSP association with clinicopathological features, including microvessel count, regarding prognostic significance was examined. Expression of TSP-1 and TSP-2 were assessed by reverse transcriptase-polymerase chain reaction in 18 normal endometrium and 55 endometrial cancer samples. Microvessel counts were determined by immunostaining for factor VIII-related antigen in endometrial cancer specimens. TSP-1 expression of secretory phase endometrium was markedly higher than that of proliferative phase endometrium (p=0.047). Expression of TSP-1 and TSP-2 was detected in 33 (60.0%) and 15 cases (27.3%), respectively, of 55 endometrial cancer samples. TSP-1 expression was significantly higher in tumors recovered from elderly women (p=0.009). TSP-2 expression was significantly higher in malignancies exhibiting cervical and lymph-vascular space involvement (p=0.029 and p=0.009, respectively). Although not statistically significant, microvessel counts were higher in cases displaying increased TSP-1 expression. The microvessel count in patients with TSP-2 expression was markedly higher than that observed in patients lacking TSP-2 expression (p=0.026). Subjects demonstrating TSP-2 mRNA expression displayed significantly poorer prognosis than those lacking TSP-2 mRNA expression (p=0.016). There was no association between TSP-1 mRNA expression and patient outcome. Our findings provide evidence that elevated TSP expression may be associated with an angiogenic phenotype in endometrial cancer. In addition, TSP-2 expression is a marker for poor prognosis in this disease.
Seki
N
N
Department of Obstetrics and Gynecology, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Kodama
J
J
Hashimoto
I
I
Hongo
A
A
Yoshinouchi
M
M
Kudo
T
T
D001808:Blood Vessels / Q000473:pathology; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019700:Thrombospondin 1 / Q000235:genetics*; D019699:Thrombospondins / Q000235:genetics*; D000099262:Thrombospondin 2
D012333:RNA, Messenger; D019700:Thrombospondin 1; D019699:Thrombospondins; D000099262:Thrombospondin 2