Primary osteosarcoma of ovary.

Primary osteosarcoma originating from the ovary is an exceedingly rare, highly malignant tumor. Only a few cases have been reported in the past few decades. We describe a 50-year-old postmenopausal woman who presented with a large abdominal mass. The clinical diagnosis was malignant ovarian cancer. Her disease was aggressive; she had no response to systemic chemotherapy and died within 1 month of presentation. A definitive diagnosis of primary ovarian osteosarcoma was made by histopathological examination of autopsy specimens. Although rare, primary ovarian osteosarcoma should be considered in the differential diagnosis of a large, rapidly progressing pelvic mass in a postmenopausal woman. Early diagnosis provides hope of a complete surgical resection, which is currently the only promising treatment.

[A case of PEP(BEP)-resistant ovarian dysgerminoma successfully treated by VeIP therapy].

Ovarian germ cell tumors are malignant tumors which commonly develop during childhood, and which are sensitive to chemotherapy. We have had a case of germ cell tumors which showed resistance to first-line PEP(BEP)chemotherapy. As second-line chemotherapy, VeIP therapy was used, because it is possible that this therapy is effective against recurrent testicular germ cell tumors. The patient was fourteen years old. She experienced acute abdominal pain and visited the hospital, where she was diagnosed with torsion of an ovarian tumor. An emergency laparotomy and right salpingoophorectomy were performed, the pathological diagnosis being stage Ia ovarian dysgerminoma G1. She was followed for two years until her serum hCG-CTP elevated to 1.4 mIU/mL. An MRI revealed an abnormal signal in the left ovary, so we diagnosed this as a recurrence of the dysgerminoma. Then she received chemotherapy PEP(BEP), but after eight months of PEP (BEP), her serum hCG-CTP was again elevated to 14.5 mIU/mL. A recurrence was detected with an MRI and PET-CT, and another laparotomy was performed. The recurrent region was detected in the left ovary. A left ovarian cystectomy was performed in which CDDP ip was used. After the operation, the patient again underwent chemotherapy. VeIP (vinblastine+ifosfamide+cisplatin)was chosen as the second-line regimen. After 6 courses of this therapy, she had a follow-up operation. No recurrence region was found in the pelvic area. She remains without recurrence of this disease 24 months after VeIP therapy. This case suggests that VeIP therapy might be an effective second-line therapy for patients with PEP(BEP)-resistant ovarian dysgerminoma.

Expression of a BTB/POZ protein, NAC1, is essential for the proliferation of normal cyclic endometrial glandular cells and is up-regulated by estrogen.

PURPOSE: The purpose of this study was to investigate the expression and localization of NAC1, a member of the BTB/POZ gene family in the human cyclic endometrium. EXPERIMENTAL DESIGN: NAC1 expression in normal cyclic endometrium was assessed by immunohistochemistry, and data on clinical variables were collected by retrospective chart review. To elucidate the molecular mechanisms of NAC1 expression in the normal endometrium endometrial carcinoma cell lines (Ishikawa, HHUA; ER+, PR+) and primary cultured normal endometria were tested in a sex steroid induction assay and a NAC1 knockdown assay using siRNA. RESULTS: Expression of NAC1 in glandular cells was significantly higher in the early and mid proliferative phases than in the other menstrual phases. Both NAC1 RNA and protein expression were up-regulated by treatment with 10 nmol/L 17beta-Estradiol (E2) in Ishikawa, HHUA and primary cultured normal endometrial cells. The estrogen receptor antagonist ICI 182,780 significantly attenuated E2-induced NAC1 expression. NAC1 gene knockdown inhibited cell growth and induced apoptosis in Ishikawa, HHUA, and normal endometria, all of which expressed NAC1. Furthermore, NAC1 siRNA significantly abrogated estrogen-driven cellular proliferation in Ishikawa, HHUA, and primary cultured normal endometrial cells, whereas the control siRNA had no effect on cell growth in any of these cells. CONCLUSIONS: These findings suggest that NAC1 is functionally involved in E2-induced cell growth of the normal endometrial glandular cells. Because NAC1 is thought to have oncogenic potential, the current findings may provide new insight into the mechanism of estrogen induced endometrial carcinogenesis.

Microwave endometrial ablation as an alternative to hysterectomy for the emergent control of uterine bleeding in patients who are poor surgical candidates.

BACKGROUND: Microwave endometrial ablation is a new, minimally invasive treatment option for menorrhagia. Its popularity in many countries is increasing due to its safety and simplicity. CASES: We treated menorrhagia due to submucosal myomas in two patients with a modified microwave endometrial ablation device. Surgery was contraindicated in the first patient secondary to medical co-morbidities and in the second patient because of acute hemorrhagic shock. In both cases, the operation was highly effective and each patient was satisfied with her treatment outcome. CONCLUSION: Given its safety, simplicity, and effectiveness, microwave endometrial ablation may be widely adopted for the emergent control of uterine bleeding in patients with poor surgical candidates.

[Two cases of endometrial stromal sarcoma (ESS) in which survival was prolonged by administration of MPA].

Endometrial stromal sarcoma (ESS) is very rare. It accounts for 0.5% of all uterine corpus malignant tumors and 10% of all malignant non-epithelial tumors. MPA is one effective hormonal treatment for ESS. We describe two cases in which patients with metastatic low-grade ESS lesions had prolonged survival with MPA therapy. Case 1 was a 50-year-old woman with a low-grade uterine endometrial stromal tumor who had been operated on at another hospital. She had been followed for three years. She had pelvis metastases with infiltration into the bladder, and pulmonary metastases. She had an incomplete response to chemotherapy. We initiated MPA therapy, which resulted in significant improvement in her metastatic lesions. Case 2 was a 58-year-old woman with stage Ic low-grade ESS who presented with abnormal uterine bleeding. Following surgery (TAH+BSO), MPA therapy was initiated and she had no recurrence. After 1 year and 7 months, she discontinued the MPA because it worsened her articular rheumatism. Her cancer recurred with pelvic and paraaortic lymph node metastasis. She was treated with chemotherapy, MPA and radiotherapy. Her metastases improved, and the patient has continued to survive on MPA therapy alone. These cases suggest that MPA might be an effective hormonal therapy for patients with low-grade ESS.

A BTB/POZ gene, NAC-1, a tumor recurrence-associated gene, as a potential target for Taxol resistance in ovarian cancer.

PURPOSE: We previously determined that NAC-1, a transcription factor and member of the BTB/POZ gene family, is associated with recurrent ovarian carcinomas. In the current study, we investigated further the relationship between NAC-1 expression and ovarian cancer. EXPERIMENTAL DESIGN: NAC-1 expression was assessed by immunohistochemistry, and clinical variables were collected by retrospective chart review. SiRNA system and NAC-1 gene transfection were used to asses NAC-1 function in Taxol resistance in vivo. RESULTS: Overexpression of NAC-1 correlated with shorter relapse-free survival in patients with advanced stage (stage III/IV) ovarian carcinoma treated with platinum and taxane chemotherapy. Furthermore, overexpression of NAC-1 in primary tumors predicted recurrence within 6 months after primary cytoreductive surgery followed by standard platinum and taxane chemotherapy. NAC-1 expression levels were measured and compared among the human ovarian cancer cell line (KF28), cisplatin-resistant cell line (KFr13) induced from KF28, and paclitaxel-resistant cell lines (KF28TX and KFr13TX) induced by exposing KF28 and KFr13 to dose-escalating paclitaxel. Overexpression of NAC-1 was observed in only the Taxol-resistant KF28TX and KFr13 TX cells but not in KF28 or cisplatin-resistant KFr13 cells. To confirm that NAC-1 expression was related to Taxol resistance, we used two independent but complementary approaches. NAC-1 gene knockdown in both KF28TX and KFr13TX rescued paclitaxel sensitivity. Additionally, engineered expression of NAC-1 in RK3E cells induced paclitaxel resistance. CONCLUSIONS: These results suggest that NAC-1 regulates Taxol resistance in ovarian cancer and may provide an effective target for chemotherapeutic intervention in Taxol-resistant tumors.

Expression of the bric-a-brac tramtrack broad complex protein NAC-1 in cervical carcinomas seems to correlate with poorer prognosis.

PURPOSE: Recent studies have suggested a novel oncogenic role of a bric-a-brac tramtrack broad complex (also known as POZ) domain gene, NAC-1, in ovarian carcinomas. The aim of this study was to clarify the functional role of NAC-1 in human cervical carcinomas. EXPERIMENTAL DESIGN: NAC-1 expression in cervical cancer was assessed by immunohistochemistry, and data on clinical variables were collected by retrospective chart review. NAC-1 gene knockdown using small interfering RNA and a NAC-1 gene transfection system were used to asses NAC-1 function in cervical cancer in vivo. RESULTS: Immunohistochemical and gene expression analysis revealed that NAC-1 is significantly overexpressed in cervical adenocarcinomas and adenosquamous carcinomas compared with squamous cell carcinomas. Patients with squamous cell carcinomas positive for NAC-1 expression who received radiotherapy had significantly shorter overall survival than peers whose tumors did not express NAC-1, and multivariate analysis showed that NAC-1 expression was an independent prognostic factor for overall survival after radiotherapy. Overexpressions of the NAC-1 gene stimulated cell proliferation in cervical carcinoma cells of the TCS, CaSki, and HeLa P3 lines, which do not have endogenous NAC-1 expression. NAC-1 gene knockdown inhibited cell growth and induced apoptosis in HeLa, HeLa TG, and ME180 cells, all of which overexpressed NAC-1. CONCLUSIONS: Our findings suggest that NAC-1 may play an important role in cervical carcinomas; moreover, these findings provide a rationale for future development of NAC-1-based therapy for cervical carcinomas that overexpress this candidate oncogene.

Genetic classification of ovarian carcinoma based on microsatellite analysis: relationship to clinicopathological features and patient survival.

Ovarian carcinomas can progress through two pathways of genomic instability: chromosomal instability (CIN) and microsatellite instability (MSI). However, it is unknown whether these two mechanisms could be distinguished from each other in the molecular characteristics in ovarian carcinomas. We hypothesized that these two pathways are not always independent in ovarian carcinomas. We classified 51 ovarian carcinomas based on their MSI and CIN status using microsatellite analysis and assessed whether these carcinogenic pathways affect the clinicopathological features and patient survival. Of the 51 cases, 77.4% of the tumors were microsatellite stable (MSS), 5.9% were MSI-Low (MSI-L) whilst, 16.7% were MSI-High (MSI-H). Overall, 56.8% of the tumors had at least one loss of heterozygosity (LOH) event, i.e., 56.8% CIN. Notably, we identified a significant degree of overlap between the MSI and CIN pathways. Of the 34 tumors with LOH events (CIN), 5 (14.7%) were MSI-H. In addition, of the 7 tumors that were MSI-H, 5 (71.4%) had one or more LOH events (CIN). We also identified a group of 29.4% of all tumors that did not demonstrate any evidence of either of the two pathways of genomic instability as they were MSS/MSI-L with no evidence of LOH events (CIN negative). Furthermore, patients with CIN with MSS/MSI-L have a significantly shorter overall survival compared to those in other genetic categories (P=0.019). Cox regression analysis revealed that tumors with CIN with MSS/MSI-L exhibit a poor prognostic outcome after adjustment for FIGO stage and grade. These findings suggest that some ovarian carcinomas have a significant degree of overlap between the two pathways of genomic instability and that the genetic classification using microsatellite markers may represent a potential new biomarker of risk prediction in ovarian carcinoma.

Endometrial carcinosarcoma presenting as a tibial metastasis.

Metastasis to a lower-extremity bone is an extremely rare event in patients with endometrial carcinoma. A 64-year-old woman presented with progressive right leg pain but no gynecologic complaints. A diagnostic workup revealed primary endometrial carcinosarcoma with an isolated tibial metastasis. Though the patient received only local irradiation to the tibial lesion, complete resolution of symptoms resulted. Six months after the radiotherapy, the intraabdominal disease progressed and the patient died. We note that tibial metastasis is one of the possible presenting symptoms in patients with endometrial malignant tumors. Irradiation can improve their quality of life and so may be effective in the management of symptomatic tibial metastasis.