Tadayuki Kanai

Conservative surgery for malignant ovarian tumor in women of childbearing age

AbstractBackground. The traditional operative procedures for the treatment of ovarian cancer have been simple total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. However, young patients who want to preserve fertility are occasionally encountered. This study was designed to assess the results of conservative surgical management for young women with stage I epithelial ovarian carcinoma or malignant germ cell tumor and to explore the indications for such surgical treatment. Methods. Fifty-eight patients aged under 35 years were treated for malignant ovarian tumors (germ cell tumor, n = 20; epithelial tumors, n = 38) between 1971 and 1996. We studied all 20 patients with germ cell tumors and 22 pa-tients with stage I epithelial tumors; we excluded the 12 patients with stage II and more advanced disease and the 4 patients with stage I clear cell carcinoma, because these patients had poor prognoses. Eleven of the 22 patients with stage I epithelial tumors and 8 of the 20 patients with germ cell tumors received conservative surgery (conservative surgery group); the remaining 23 patients underwent radical surgery, including hysterectomy and bilateral salpingo-oophorectomy (radical surgery group). The overall survival rates of the two groups were compared, and ovarian function and pregnancy outcome were evaluated in the conservative surgery group. Results. Of the patients with malignant epithelial tumor who were treated with conservative surgery, 3 patients with stage Ic mucinous adenocarcinoma died 1 year and 8 months, 7 years and 6 months, and 8 years, respectively, after the initial surgery. The 10-year survival rate was 65% for the conservative surgery group and 91% for the radical surgery group. All patients with stage Ia epithelial tumors in both groups survived, and there were no differences in survival curves between the two groups among the patients with stage Ic epithelial tumors. All patients with germ cell tumors in the conservative surgery group survived. Their survival rate, however, was not significantly better than that in the radical surgery group. All patients with germ cell tumors who received platinum-based chemotherapy survived and had a significantly better survival rate than those who received non-platinum-based regimens (P < 0.05). All the patients in the conservative surgery group received postoperative chemotherapy; 10 of these patients had transient ovulation failure after the completion of chemotherapy, although a normal menstrual cycle was restored within 1 year. Of the 10 patients who wished to have babies, 6 became pregnant, and they have had a total of 11 children. Conclusion. Conservative surgery is feasible in patients with stage Ia epithelial carcinoma and germ cell tumor. Postoperative chemotherapy suppressed ovarian function in these patients, but only for a brief period.

Expression of Cell Cycle Regulators in Endometrial Adenocarcinoma

Abnormal expressions of cell cycle regulators, such as cyclin-dependent kinases (cdk), cyclins, and cyclin kinase inhibitors, are supposed to play an important role in the tumorigenesis and progression of carcinoma. The aim of the present study was to investigate the correlation of the expression of these cell cycle regulators with proliferative activity and clinicopathological parameters in endometrial adenocarcinoma, and the regulation of these proteins by sex steroid hormones in endometrial cancer cells. Tissue samples of 127 endometrial adenocarcinomas (endometrioid type) were used in the present study. Immunohistochemical staining of cycle regulators was performed according to the labeled streptavidin-biotin method. Ishikawa cells, in which estrogen receptor (ER) cDNA was transfected by the SuperFect method, and HEC-265 cells positive for the progesterone receptor were used in an in vitro study. Quantitative analysis of proteins was performed by immunoblotting. Expression of cyclin D1, cyclin E, cyclin A, p53, and p27 was positively correlated with Ki-67 expression. Expression of cdk2, cyclin Dl, cyclin E, cyclin A, p53, and p27 was positively associated with histological grade. Expression of cyclin E was significantly correlated with lymphovascular space involvement (LVSI) and myometrial invasion, and expression of cyclin A was correlated with LVSI and group (coexistence with or without hyperplasia). p53 was related with stage, LVSI, myometrial invasion, and group; whereas p27 was correlated with stage, LVSI, and lymph node metastasis. Estradiol (E2) revealed a stimulatory effect on the growth of ER-transfected Ishikawa cells, in addition to enhancing their expression of cyclin A and cyclin E. In contrast, medroxyprogesterone acetate (MPA) suppressed HEC-265 cell growth after its accumulation of p27 in the cells. In conclusion, the expression of cell cycle regulators was significantly associated with cell proliferation, histological grade, and some clinicopathological parameters in endometrial adenocarcinoma. A cell line stably sensitive to E2 was established after ER cDNA was transfected into Ishikawa cells, and cyclin A and E may be involved in the enhanced cell growth induced by E2. p27 accumulation induced by MPA may be involved in the progesterone-induced growth suppression of endometrial cancer cells.