Expression of angiogenic factors and apoptotic factors in leiomyosarcoma and leiomyoma.
Angiogenesis is essential for tumor growth and metastasis. Some angiogenic factors, such as vascular endothelial growth factor (VEGF), platelet-derived endothelial cell growth factor (PD-ECGF), transforming growth factor-alpha (TGF-alpha) and basic fibroblast growth factor (bFGF) are involved in increased angiogenic activity and disease progression in many carcinomas. However, there is little information regarding the association between angiogenic factors and leiomyosarcoma. Although there are abundant vessels in the sarcoma which enable it to easily receive nutrition and medicinal components, chemotherapy cannot effectively treat leiomyosarcoma. This means the resistance to anticancer drugs in leiomyosarcoma is very strong. However, the resistant mechanism is still unclear. In this study, expressions of VEGF, PD-ECGF, TGF-alpha, bFGF, intratumoral microvessel density (IMVD), and p53, Bcl-2 and Bax were examined by immunohistochemistry in 30 patients with leiomyosarcoma and 21 patients with leiomyoma. With regard to angiogenesis, PD-ECGF and TGF-alpha were closely associated with an increase in IMVD (p=0.012, 0.0196, respectively), and VEGF and PD-ECGF were significantly expressed in leiomyosarcoma compared with leiomyoma (p=0.041, 0.041, respectively). Although p53 expression in leiomyosarcoma was significantly higher than in leiomyoma (p=0.016), the frequency of p53 positivity was not so high (47%). On the other hand, the ratio of Bcl-2/Bax in leiomyosarcoma was significantly higher than that in leiomyoma (p=0.033). The findings of this study suggest that in leiomyosarcoma, angiogenic factors, such as PD-ECGF, VEGF and TGF-alpha expression may be involved in tumor angiogenesis, and the frequently high ratio of Bcl-2/Bax and expression of p53 gene mutation might be related to chemoresistance mechanism.
Hong
T
T
Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Shimada
Y
Y
Uchida
S
S
Itami
A
A
Li
Z
Z
Ding
Y
Y
Kaganoi
J
J
Komoto
I
I
Sakurai
T
T
Imamura
M
M
D043925:Angiogenesis Inducing Agents / Q000096:biosynthesis*; D017209:Apoptosis; D004067:Digestive System Neoplasms / Q000378:metabolism* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D006801:Humans; D007889:Leiomyoma / Q000378:metabolism* / Q000473:pathology; D007890:Leiomyosarcoma / Q000378:metabolism* / Q000473:pathology; D008222:Lymphokines / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D013939:Thymidine Phosphorylase / Q000096:biosynthesis; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D051028:bcl-2-Associated X Protein
D043925:Angiogenesis Inducing Agents; C494826:BAX protein, human; D016228:Endothelial Growth Factors; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016211:Transforming Growth Factor alpha; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D051028:bcl-2-Associated X Protein; D016222:Fibroblast Growth Factor 2; D013939:Thymidine Phosphorylase