Endometrial cancer is a hormone-dependent malignancy, and the majority has a precursor phase of endometrial hyperplasia. Histologic subtypes have been recognized with differing natural history. The relationship between hormone response, histology, and molecular profile is not established, but the relevant biology is summarized. This study was a systematic review of the literature to identify which populations should be considered for hormone interventions. Systematic searches were carried out in the English literature for randomized controlled trials and phase II studies of hormone interventions in endometrial cancer. Five randomized trials and 29 phase II studies were identified comprising a total of 2471 patients. In previously untreated patients with grade 1 (G1) or G2 tumors, the response rate for progestogens and the progression-free survival is in the range of 11-56% and 2.5-14 months, respectively. Higher response rates are seen in progesterone receptor-positive cases. Phase II studies comprise the majority of the data and many are of poor quality. There was considerable heterogeneity in patient selection, prior treatment, and type of regimen, and meta-analysis was not possible. G3 or G4 toxicity was less than 5%. We conclude that hormone receptor assessments should be carried out in all patients entered on clinical trials and may aid clinical management in selected cases. Receptor-negative status should not be an absolute contraindication to hormone intervention. Integration of hormone treatment with conventional chemotherapy and growth factor-targeted therapy needs to be explored.

Summary Glutathione S-transferase sub-types a, 1t and were assessed by immunocytochemistry in 109 biopsies of ovarian tissue, comprising malignant epithelial tissue in 86 cases and tissue of ovarian origin considered to be normal in 23. Glutathione S-transferase n was the most prevalent, being present in all except one malignant epithelium studied and 83% of non-malignant tissue. There were no significant differences in the overall distribution of positive staining for a, and in the malignant and non-malignant biopsies, although the intensity of staining was greater in the malignant epithelium. Stromal staining was in general more pronounced in the malignant biopsies, and this was particularly prominent in the case of the a sub-type. Positive staining was seen more frequently in the less well-differentiated tumours, and a diffuse cytoplasmic pattern was the most common observation in tumours of moderate and poor differentiation. There was no significant association between survival and the presence or absence of sub-type staining of a and sub-type. For the sub-type at, patient survival was found to correlate with the intensity of staining (on a 0-+ + + scale). Those patients showing resistance to cytotoxic chemotherapy were found to have a higher intensity of staining for GSTi than responding patients.

We report on a 49-year-old woman with relapsing ovarian cancer who developed a hypersensitivity reaction (HSR) to carboplatin and, subsequently, to cisplatin. This patient was known to be allergic to Co-Amoxiclav and talc, both giving rise to a transient macular skin rash, but had no other history of atopy. Similar cases, including some of life-threatening severity, have been reported in the literature. These severe reactions may prevent a small population of young patients from receiving effective therapy with cisplatin or its analogues, treatment known to be associated with a significant improvement in survival in germ-cell tumours, ovarian cancer and osteogenic sarcoma.

COX-1 and COX-2 are members of the cyclooxygenase (COX) family, which influence tumor invasion and apoptosis. The objective of the study was to assess the relationship between COX-1 and COX-2 expression in early-stage disease and subsequent disease relapse and long-term survival. Women with FIGO stage I and II cervical carcinoma, younger than 50 years, treated between 1981 and 1990 were included. COX-1 and COX-2 expressions in the tumors were assessed by immunohistochemistry. COX-1 and COX-2 were expressed in 61% (17/28) and 57% (16/28) of tumors, respectively. COX-1 nonexpressers showed an improved overall survival compared to expressers (log-rank test, P= 0.09). There was no significant difference in the overall survival in COX-2 nonexpressers compared to expressers (P= 0.6). Out of eight women with disease relapse, COX-1 or COX-2 expression was noted in six of eight tumors, and both were expressed in five of eight tumors. Our preliminary data suggest an adverse prognosis with COX-1 expression in early-stage cervical carcinoma and a trend toward COX-1 expression in disease relapse. The association between COX-2 expression and a worse prognosis was not proven in this study.

5501 Background: The Dual specificity phosphatases (DUSPs) are a subclass of the protein tyrosine phosphatase (PTP) gene family which appears to be selective for dephosphorylating the critical phosphothreonine and phosphotyrosine residues within the mitogen-activated protein kinases (MAPKs) leading to inactivation. MAPK activation is a downstream target of several oncogenes and may give rise to oncogenic transformation, and hence DUSPs are potential tumor suppressor genes. The aim of this study was to investigate if DUSPs are subject to methylation-dependent silencing in epithelial ovarian cancer. Methods: In this study, promoter methylation and gene expression of the DUSPs genes (DUSP1, DUSP2, DUSP3, DUSP4, DUSP5, DUSP6, DUSP7, DUSP8 and DUSP10) were investigated in 9 ovarian cancer cell lines and in 74 primary epithelial ovarian tumors (Stage III/IV), using methylation specific PCR (MSP) and Reverse- transcription PCR (RT-PCR). The 74 clinical samples were retrospectively retrieved from a large Phase III RCT (the EORTC 55931/NCIC OV10) with clinical follow-up in excess of 6.5 years. Results: Ovarian Cancer Cell lines: Aberrant CpG methylation detected in DUSP1, DUSP2, DUSP4, DUSP6, DUSP7 and DUSP8. DUSP7 promoter methylation was associated with downregulation of mRNA expression. Primary Ovarian Tumors: Methylation of DUSP1, DUSP2, DUSP7 and DUSP8 was observed in 15–38% of the primary tumors. DUSP7 methylation is a predictor of adverse PFS in both univariate (median PFS 10.6 m versus 13.3m, p=0.002) and multivariate (Cox Regression HR 2.76, p<0.001) analyses, and is associated with a trend for poorer OS (22.1 m versus 29.3 m, p=0.07). In contrast, DUSP8 methylation is an independent predictor of favorable PFS (median 23.7m versus 11.5m; Cox Regression HR 0.30, p=0.006) and OS (HR 0.31, p=0.013). 5-year OS for DUSP8 methylated patients was 58.3% compared with 16.1% for DUSP8 unmethylated (HR 0.277, p=0.005). Conclusion: This is the first report of DUSP methylation in epithelial ovarian cancer. The study suggests that methylation-dependent transcriptional silencing of DUSP7 in advanced epithelial ovarian cancer may represent an independent predictor of adverse PFS. DUSP8 methylation, on the other hand, is a favorable clinical outcome marker. No significant financial relationships to disclose.