Recurrent endometrial cancer: a retrospective study.

OBJECTIVE: The value of follow-up after treatment for endometrial cancer will be discussed. STUDY DESIGN: We evaluated our clinical experience, including mode of detection, of patients with recurrent endometrial cancer treated in the Erasmus Medical Centre in Rotterdam over a 20-year period. Clinical data and histopathological features from 64 patients were analyzed. Survival was analyzed with a Kaplan-Meier curve. RESULTS: Twenty-two patients had a local recurrence, 30 had a distant recurrence and 12 had simultaneous local and distant recurrent disease. Ninety-five percent of the local recurrences and 67% of the distant recurrences were detected within three years. Twenty-seven patients had a screen-detected recurrence, 34 had an interval screening recurrence and two had a chance finding recurrence. The overall survival rate at two years was 70% and at five years 53%. Patients with a screen-detected recurrence had a 5-year survival rate of 62%, while patients with interval screening and chance finding recurrences had a 5-year survival rate of 47%. CONCLUSION: A follow-up program in the first three years after primary treatment of endometrial cancer is useful in detecting recurrent disease. We have no reason to use a different program of follow-up in patients with low risk primary disease.

Alterations in the p53 pathway and prognosis in advanced ovarian cancer: a multi-factorial analysis of the EORTC Gynaecological Cancer group (study 55865).

PURPOSE: The study was designed to determine independent prognostic variables in suboptimally debulked advanced ovarian cancer patients entered in the randomised phase III study EORTC 55865. EXPERIMENTAL DESIGN: Retrospectively collected paraffin blocks from 169 patients with stages IIb-IV epithelial ovarian cancer, taken at primary debulking surgery, were analysed. All patients were treated with cyclophosphamide and cisplatin (CP), and followed up for a median of 10 years. Expression of p53, bcl-2, P21, Ki-67 and HER-2 status was assessed by immunohistochemistry (IHC). RESULTS: Expression of p21, a downstream effector of the p53 gene, was found to be a favourable prognostic factor for survival (HR 0.58, CI 0.36-0.94, p=0.025) in addition to FIGO stage (HR 1.54, CI 1.08-2.21, p=or<0.02). For progression free survival (PFS), both p21 (HR 0.52) and Ki-67 (HR 0.6) were significant factors. CONCLUSION: P21 overexpression is a positive prognostic factor for survival and PFS in advanced ovarian carcinoma with residual lesions of more than 1 cm.

Epithelioid trophoblastic tumour: a case report and review of the literature.

Epithelioid trophoblastic tumour (ETT) is an unusual type of trophoblastic tumour, which can cause difficulties in diagnosis and (as a consequence) in treatment. The literature suggests that surgery should be the treatment of choice for ETT as it is not responsive to chemotherapeutic agents, used in the treatment of other types of gestational trophoblastic diseases. This case report describes an ETT, which was initially diagnosed as a carcinoma of the cervix. Surgical management was chosen based on the literature. 6 months later the patient also developed a plasmacytoma and was treated with radiotherapy. The occurrence of ETT and plasmacytoma in combination has never been described before. This case report describes a rare case of an atypical trophoblastic tumour, with problematic differential diagnosis. Treatment of carcinoma of the cervix would have necessitated postoperative radiotherapy, but on diagnosis of ETT, surgical management was considered sufficient. Hence, it is important to consider the occurrence of ETTs, although rare, in patients with atypical cervical or endometrial cancer, and in patients diagnosed with a gestational trophoblastic tumour, who do not respond to appropriate chemotherapy.

Tamoxifen treatment for breast cancer enforces a distinct gene-expression profile on the human endometrium: an exploratory study.

Tamoxifen treatment for breast cancer increases proliferation of the endometrium, resulting in an enhanced prevalence of endometrial pathologies, including endometrial cancer. An exploratory study was performed to begin to understand the molecular mechanism of tamoxifen action in the endometrium. Gene-expression profiles were generated of endometrial samples of tamoxifen users and compared with matched controls. The pathological classification of samples from both groups included atrophic/inactive endometrium and endometrial polyps. Unsupervised clustering revealed that samples of tamoxifen users were, irrespective of pathological classification, fairly similar and consequently form a subgroup distinct from the matched controls. Using SAM analysis (a statistical method to select genes differentially expressed between groups), 256 differentially expressed genes were selected between the tamoxifen and control groups. Upon comparing these genes with oestrogen-regulated genes, identified under similar circumstances, 95% of the differentially expressed genes turned out to be tamoxifen-specific. Finally, construction of a gene-expression network of the differentially expressed genes revealed that 69 genes centred around five well-known genes: TP53, RELA, MYC, epidermal growth factor receptor and beta-catenin. This could indicate that these well-known genes, and the pathways in which they function, are important for tamoxifen-controlled proliferation of the endometrium.

A shift to a peripheral Th2-type cytokine pattern during the carcinogenesis of cervical cancer becomes manifest in CIN III lesions.

BACKGROUND: A shifted balance between T helper 1 (Th1)-type and Th2-type cytokines has been hypothesised in cervical dysplasia. AIMS: To evaluate possible deregulation of the cytokine network by estimating the expression of peripheral cytokines in different stages of cervical disease and in relation to the presence or absence of high risk human papillomavirus (HR-HPV). METHODS: Twenty one HR-HPV positive women with high grade cervical intraepithelial neoplasia (CIN II-III) and 12 patients with invasive cervical carcinoma formed the study groups. Two control groups consisted of 10 HR-HPV positive and 11 HR-HPV negative women without CIN. Differences in leucocyte subgroups were evaluated by a differential leucocyte count. Plasma concentrations of tumour necrosis factor alpha (TNFalpha), TNFalpha receptors TNFRI and TNFRII, interferon gamma (IFNgamma), interleukin 2 (IL-2), IL-12, IL-4, and IL-10 were determined by enzyme linked immunosorbent assays. RESULTS: Leucocyte counts in patients with CIN III and carcinoma were significantly higher than in controls. Plasma IFNgamma concentrations were significantly lower in patients with CIN III and carcinoma than in women with CIN II or controls. Plasma concentrations of IL-12, IL-2, IL-4, and TNFalpha did not differ significantly between groups, but significantly lower plasma concentrations of TNFRII were found in CIN III and carcinoma compared with CIN II. IL-10 was detected with increased frequency in the plasma of patients with CIN III and carcinoma. CONCLUSIONS: These results indicate that a shift to a Th2-type cytokine pattern during the carcinogenesis of cervical cancer occurs in women with CIN III lesions.

Stage III and IV endometrial cancer: a 20-year review of patients.

In advanced endometrial cancer, the importance of peritoneal cytology and optimal surgical cytoreduction remain subjects of discussion. We evaluated our clinical experience of 67 patients with FIGO stage III and IV endometrial cancer treated in the Erasmus Medical Centre in Rotterdam over a 20-year period with an emphasis on stage IIIA disease based on positive cytology only and optimal cytoreduction. Lymphadenectomy was not routinely performed and peritoneal cytology was examined in 74% of the patients. Stage IIIA disease was found in 33 patients, 10 of whom had positive cytology only. Analysis showed that incidence of recurrence and survival rates of patients with stage IIIA disease based on positive cytology only were comparable with stage IIIA disease based on other factors. In 50 patients, it was possible to remove all macroscopic tumor, whereas in 17 patients, an optimal cytoreduction was not achievable. The 2- and 5-year survival rates after optimal cytoreduction were 82.2% and 65.6%; where this could not be achieved, these figures were 50.8% and 40.6%. In advanced endometrial cancer patients, positive peritoneal cytology seems an important prognostic factor in stage IIIA disease if lymph node status is unknown. Survival is improved if optimal surgical cytoreduction is achievable.