Expression of the Endostatin gene in epithelial ovarian cancer

Endostatin, a M-r 20,000 COOH-terminal fragment of collagen XVIII, is curre ntly in preclinical development as a novel antiangiogenic agent. The gene e xpression of this molecule in 23 normal ovaries with follicle or corpus lut eum and in 64 cases of epithelial ovarian cancer (27 serous, 18 mucinous, 1 3 endometrioid, 4 clear cell, and 2 undifferentiated carcinomas) was analyz ed by PCR of RNA after reverse transcription. Seven of the cases were of lo w 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 dise ase. 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-mic roglobulin gene. Endostatin gene expression in ovarian cancers (median, 0.1 4; range, 0.02-1.11) was significantly higher than that in normal ovaries w ith 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 g ene expression; however, other clinico pathological features (e.g., patient age at diagnosis, histological subtype, and histological grade) were not s ignificantly 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 (greater than or equal to 0.14)] to be significant ly worse than that of patients with low endostatin gene expression [less th an the median (< 0.14); P = 0.044]. Our results with regard to the gene exp ression 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.