Expression of the Endostatin gene in epithelial ovarian cancer.
Endostatin, a M(r) 20,000 COOH-terminal fragment of collagen XVIII, is currently in preclinical development as a novel antiangiogenic agent. The gene expression of this molecule in 23 normal ovaries with follicle or corpus luteum and in 64 cases of epithelial ovarian cancer (27 serous, 18 mucinous, 13 endometrioid, 4 clear cell, and 2 undifferentiated carcinomas) was analyzed by PCR of RNA after reverse transcription. Seven of the cases were of low malignant potential. With regard to staging, 23 cases had stage I disease, 5 had stage II disease, 29 had stage III disease, and 7 had stage IV disease. The level of endostatin gene expression was described in terms of the ratio of the relative yield of the endostatin gene to that of the beta2-microglobulin gene. Endostatin gene expression in ovarian cancers (median, 0.14; range, 0.02-1.11) was significantly higher than that in normal ovaries with follicle or corpus luteum (median, 0.08; range, 0.03-0.26; P = 0.009). International Federation of Gynecology and Obstetrics stage (P = 0.009) and residual tumor (P = 0.005) were significantly associated with endostatin gene expression; however, other clinicopathological features (e.g., patient age at diagnosis, histological subtype, and histological grade) were not significantly associated with endostatin gene expression. Survival data were available for all patients. Univariate Cox regression analysis showed the prognosis of the patients with high endostatin gene expression [equal to or greater than the median (> or =0.14)] to be significantly worse than that of patients with low endostatin gene expression [less than the median (<0.14); P = 0.044]. Our results with regard to the gene expression of this endogenous inhibitor of angiogenesis present a new insight to understand the biology of epithelial ovarian cancer and may lead to the development of a new therapeutic strategy for epithelial ovarian cancer.
Hata
K
K
Department of Obstetrics and Gynecology, Shimane Medical University, Izumo 693-8501, Japan. hata31@shimane-med.ac.jp
Fujiwaki
R
R
Nakayama
K
K
Miyazaki
K
K
D003094:Collagen / Q000235:genetics*; D043170:Collagen Type XVIII; D043169:Endostatins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D010446:Peptide Fragments / Q000235:genetics*; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
D043170:Collagen Type XVIII; D043169:Endostatins; D010446:Peptide Fragments; D012334:RNA, Neoplasm; D003094:Collagen