Harmonisation of biobanking standards in endometrial cancer research.

BACKGROUND: Endometrial cancer is the most common gynaecological cancer and its incidence is predicted to escalate by 50-100% in 2025 with a parallel increase in associated mortality. Variations in the collection, processing and storage of biospecimens can affect the generalisability of the scientific data. We aimed to harmonise the collection of biospecimens, clinical data relevant to endometrial cancer and to develop standard operative procedures for the collection, processing and storage of endometrial cancer biospecimens. METHODS: We designed research tools, which were evaluated and revised through three consensus rounds - to obtain local/regional, national and European consensus. Modified final tools were disseminated to a panel (n=40) representing all stakeholders in endometrial cancer research for consensus generation. RESULTS: The final consensus demonstrated unanimous agreement with the minimal surgical and patient data collection tools. A high level of agreement was also observed for the other remaining standard tools. CONCLUSIONS: We here present the final versions of the tools, which are freely available and easily accessible to all endometrial cancer researchers. We believe that these tools will facilitate rapid progress in endometrial cancer research, both in future collaborations and in large-scale multicentre studies.

Androgen receptors are acquired by healthy postmenopausal endometrial epithelium and their subsequent loss in endometrial cancer is associated with poor survival.

BACKGROUND: Endometrial cancer (EC) is a hormone-driven disease, and androgen receptor (AR) expression in high-grade EC (HGEC) and metastatic EC has not yet been described. METHODS: The expression pattern and prognostic value of AR in relation to oestrogen (ERα and ERß) and progesterone (PR) receptors, and the proliferation marker Ki67 in all EC subtypes (n = 85) were compared with that of healthy and hyperplastic endometrium, using immunohistochemisty and qPCR. RESULTS: Compared with proliferative endometrium, postmenopausal endometrtial epithelium showed significantly higher expression of AR (P < 0.001) and ERα (P = 0.035), which persisted in hyperplastic epithelium and in low-grade EC (LGEC). High-grade EC showed a significant loss of AR (P < 0.0001), PR (P < 0.0001) and ERß (P < 0.035) compared with LGEC, whilst maintaining weak to moderate ERα. Unlike PR, AR expression in metastatic lesions was significantly (P = 0.039) higher than that in primary tumours. Androgen receptor expression correlated with favourable clinicopathological features and a lower proliferation index. Loss of AR, with/without the loss of PR was associated with a significantly lower disease-free survival (P < 0.0001, P < 0.0001, respectively). CONCLUSIONS: Postmenopausal endometrial epithelium acquires AR whilst preserving other steroid hormone receptors. Loss of AR, PR with retention of ERα and ERß may promote the unrestrained growth of HGEC. Androgen receptor may therefore be a clinically relevant prognostic indicator and a potential therapeutic target in EC.

Hormone therapy in advanced and recurrent endometrial cancer: a systematic review.

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.

Prevention of vaginal stenosis in patients following vaginal brachytherapy.

The assessment of patients following intracavitary irradiation administered as part of the treatment of gynaecological malignancy reveals vaginal stenosis in the majority. Vaginal dilators are available for daily insertion in an attempt to prevent the formation of adhesions. However, the design of the dilator neglects the fact that the vagina is the most distensible in the upper third and hence many patients develop stenosis of the upper vagina. Many clinicians have abandoned the use of dilators and instead advise patients to have sexual intercourse to prevent the problem. In 1994, we designed a new vaginal stent, which was given to all patients who had received intracavitary irradiation with full instructions about its use. This stent was designed to suit better the true anatomy of the vagina and hence, with correct use, should prevent vaginal stenosis. A retrospective study was undertaken to look at the incidence of vaginal stenosis and this was compared with the incidence in patients using the new stent. The study revealed that 57% of the patients who were advised to have sexual intercourse had stenosis, whereas 11% of the patients using the stent had evidence of stenosis, which, however, was related to their incorrect use of the stent. In those who used the stent correctly there was no evidence of vaginal stenosis. Details of the design of the stent and the problems relating to those who used the stent incorrectly are presented. The findings of this study strongly support the continued use of this vaginal stent in patients who have undergone intracavitary irradiation as a means of preventing this common complication.