Preoperative diagnosis and treatment results in 106 patients with uterine sarcoma in Hokkaido, Japan.

OBJECTIVE: The aim of this study was to evaluate the clinicopathological features of uterine sarcoma in Hokkaido, Japan, between 1990 and 1999, and to identify prognostic factors of patients with such malignancies in this area and period. METHODS: One hundred and six patients with histologically proven uterine sarcoma were evaluated retrospectively. RESULTS: 93.5% of the patients with carcinosarcoma (CS) were diagnosed as having malignant disease preoperatively, while 65% of those with leiomyosarcoma (LMS) and 75% of those with endometrial stromal sarcoma (ESS) were preoperatively diagnosed as benign leiomyoma. When patients had no residual disease postoperatively, 5-year survival rates in patients with CS and LMS were 78.8 and 73.0%, respectively. ESS cases had a better prognosis (94.7% for stage I cases). In patients with early-stage sarcoma, pelvic lymphadenectomy and adjuvant chemotherapy, with or without cis-diamminedichloroplatinum, failed to show a survival benefit in both CS and LMS cases. Distant metastasis, myometrial invasion, and no residual disease at surgery were significantly associated with risk of death or recurrence in CS and LMS cases. CONCLUSION: Accurate preoperative diagnosis of uterine sarcoma was difficult, and no residual disease at surgery was the most important prognostic factor in patients with this disease. Postoperative adjuvant therapy had little effect on survival, especially in early-stage disease.

[A pilot study of combined chemotherapy with paclitaxel, doxorubicin and cisplatin for endometrial cancer].

A pilot trial of combined chemotherapy with paclitaxel, doxorubicin and cisplatin was conducted in patients with advanced endometrial cancer. Between June 2000 and March 2002 8 patients were treated with combined chemotherapy, consisting of paclitaxel, 135 mg/m2; doxorubicin, 30 mg/m2; and cisplatin, 50 mg/m2 (TAP therapy). Patients received 3 to 5 courses of TAP therapy every 4 weeks. The major adverse effect was myelosuppression. All patients had grade 3 or 4 neutropenia, but did not have any severe infection with uncontrollable fever. Only 1 patient discontinued additional therapy due to grade 3 thrombocytopenia after 3 cycles. Grade 2 neurotoxicity occurred in 5 patients, but grade 3 was not observed. Among 5 patients with measurable tumors, 4 achieved partial response and 1 had no change of tumor size, indicating a response rate of 80.0%. We found that TAP therapy was feasible with G-CSF support and shows potential for high efficacy in advanced endometrial cancer.

Epigenetic inactivation of TMS1/ASC in ovarian cancer.

PURPOSE: The purpose of this work was to explore the role of epigenetic inactivation of apoptotic pathways in ovarian cancer by examining the DNA methylation and expression status of four proapoptotic genes in primary ovarian cancers and cancer cell lines and to correlate those findings with the clinicopathological features of ovarian cancer patients. EXPERIMENTAL DESIGN: Genomic DNA was isolated from 15 ovarian cancer cell lines, 80 primary ovarian cancer specimens, and 4 normal ovary specimens using phenol-chloroform extraction. The methylation status of the DNA was evaluated using combined bisulfite restriction analysis, gene expression was evaluated using reverse transcription-PCR, and histone acetylation was evaluated using chromatin immunoprecipitation. RESULTS: Of the four proapoptotic genes studied, expression of TMS1/ASC was absent in six ovarian cancer cell lines. Dense methylation of the 5' region of TMS1/ASC was detected in cells not expressing TMS1/ASC. Treating methylated cells with 5-aza-deoxycytidine restored gene expression, confirming the role of methylation in silencing the gene. Chromatin immunoprecipitation revealed histone to be deacetylated in cells not expressing TMS1/ASC, indicating that histone deacetylation is also involved in silencing TMS1/ASC. Aberrant methylation of TMS1/ASC was detected in 15 of 80 ovarian cancer tissues (19%) but in none of the normal ovary specimens. Aberrant methylation of TMS1/ASC was observed significantly more often in clear cell-type ovarian cancers than in other tumor types (P < 0.0001). CONCLUSIONS: Methylation-mediated silencing of TMS1/ASC confers a survival advantage to tumor cells by enabling them to escape apoptosis. The role for aberrant methylation in human ovarian tumorigenesis may be particularly important for ovarian cancers with the clear cell phenotype.

Comparison of the usefulness between a new universal grading system for epithelial ovarian cancer and the FIGO grading system.

OBJECTIVE: The aim of this study was to compare the usefulness of a new universal grading system for ovarian cancer proposed by Shimizu et al. (Cancer 82 (1998), 893; Gynecol. Oncol. 70 (1998), 2) with that of the FIGO grading system as a prognostic factor of ovarian cancer. METHODS: We reviewed all paraffin-embedded tissues of epithelial ovarian cancer obtained from 130 women who underwent initial treatment including primary surgery in our hospital between January 1990 and December 2000. The scores of the specimens were obtained according to both the universal grading system and the FIGO grading system. RESULTS: Both the FIGO grading system and the universal grading system worked as significant prognostic indicators. Patients with Grades 1 and 3 of the universal grading system had high and low 5-year survival rates, respectively, compared to those of the FIGO grading system. Inconsistencies in histologic grade between the FIGO and universal grading systems were observed in 22 patients. The positive rate of lymph node metastasis in patients with Grade 3 of the universal grading system was significantly high compared to those of the FIGO grading system (P = 0.03). Patients with Grade 3 of the universal grading system with residual tumor of not less than 2 cm in diameter were observed more frequently than those of the FIGO grading system. C4ONCLUSION: The universal grading system was superior to the FIGO grading system in terms of the prediction of malignancies such as the potential of lymph node metastasis and invasion and the adaptability to clear cell cancer.

Reproductive function after treatment of malignant germ cell ovarian tumors.

The outcome and reproductive function were examined among patients with malignant ovarian germ cell tumors treated since 1980. Between 1980 and 2001, fertility-sparing surgery was performed in 26 women, 23 of whom received adjuvant chemotherapy. With a median follow-up of 66.6 months, all patients have been alive, with histological types of 6 immature teratomas, 8 dysgerminomas, 6 yolk sac tumors, and 6 mixed types. Clinical stages were involved of 17 early stage and 9 advanced stage patients. After treatment, 20 women out of 26 recovered menstruation within 6 months. During follow-up, two chemotherapy-untreated and one treated patients experienced 4 conceptions in total. A treated patient conceived but selected artificial termination by affection of chemotherapy. Conservative surgery with adjuvant chemotherapy is the standard approach to treat patients with malignant ovarian germ cell tumors. In these 20 years, we experienced no delivery, so that fertility seems to be seriously affected by treatments.