STUDY QUESTIONIs human endometrial leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) gene expression limited to the postulated epithelial stem cell niche, stratum basalis glands, and is it hormonally regulated?SUMMARY ANSWER LGR5 expressing cells are not limited to the postulated stem cell niche but LGR5 expression is hormonally regulated.WHAT IS KNOWN ALREADYThe human endometrium is a highly regenerative tissue; however, endometrial epithelial stem cell markers are yet to be confirmed. LGR5 is a marker of stem cells in various epithelia.STUDY DESIGN, SIZE, DURATIONThe study was conducted at a University Research Institute. Endometrial samples from 50 healthy women undergoing benign gynaecological surgery with no endometrial pathology at the Liverpool Women’s hospital were included and analysed in the following six sub-categories; proliferative, secretory phases of menstrual cycle, postmenopausal, those using oral and local progestagens and samples for in vitro explant culture.PARTICIPANTS/MATERIALS, SETTING, METHODSIn this study, we used the gold standard method, in situ hybridisation (ISH) along with qPCR and a systems biology approach to study the location of LGR5 gene expression in full thickness human endometrium and Fallopian tubes. The progesterone regulation of endometrial LGR5 was examined in vivo and in short-term cultured endometrial tissue explants in vitro. LGR5 expression was correlated with epithelial proliferation (Ki67), and expression of previously reported epithelia progenitor markers (SOX9 and SSEA-1) immunohistochemistry (IHC).MAIN RESULTS AND THE ROLE OF CHANCE LGR5 gene expression was significantly higher in the endometrial luminal epithelium than in all other epithelial compartments in the healthy human endometrium, including the endometrial stratum basalis (P < 0.05). The strongest SSEA-1 and SOX9 staining was observed in the stratum basalis glands, but the general trend of SOX9 and SSEA-1 expression followed the same cyclical pattern of expression as LGR5. Stratum functionalis epithelial Ki67-LI and LGR5 expression levels correlated significantly (r = 0.74, P = 0.01), however, they did not correlate in luminal and stratum basalis epithelium (r = 0.5 and 0.13, respectively). Endometrial LGR5 demonstrates a dynamic spatiotemporal expression pattern, suggesting hormonal regulation. Oral and local progestogens significantly reduced endometrial LGR5 mRNA levels compared with women not on hormonal treatment (P < 0.01). Our data were in agreement with in silico analysis of published endometrial microarrays.LARGE SCALE DATAWe did not generate our own large scale data but interrogated publically available large scale data sets.LIMITATIONS, REASONS FOR CAUTIONIn the absence of reliable antibodies for human LGR5 protein and validated lineage markers for the various epithelial populations that potentially exist within the endometrium, our study does not formally characterise or examine the functional ability of the resident LGR5+ cells as multipotent.WIDER IMPLICATIONS OF TH...
PWE-154 The prevalence of GI malignancy ranged from 0.0% in younger females with mild anaemia, to over 25% in older males with more severe anaemia. By the pre-defined criteria, the model identified subpopulations of 84 (11% of the total) at extreme low risk, and 117 (16%) at extreme high risk. ConclusionThe results confirm previous work identifying age, sex and haemoglobin concentration as variables predictive of underlying malignancy in IDA. Furthermore, the findings suggest that over a quarter of subjects with IDA can be predicted to be of extremely low or high risk on the basis of these simple and objective clinical criteria. This may be of clinical relevance for patient counselling, prioritisation of investigations and allocation of resources. Work is ongoing to validate risk prediction in a prospective study, and to refine the model by inclusion of additional variables. Disclosure of Interest None Declared. REFEREncE ROYAL MARSDEN HOSPITAL, LONDON, UKIntroduction As new cancer treatments have been introduced, there have been enormous improvements in outcomes for treated patients. They are living longer and the number of survivors of cancer therapy is growing by 3% per year in the UK. 17 000 UK patients are treated annually with pelvic radiotherapy. 80% of patients who receive pelvic radiotherapy are left with chronic alteration in GI function and 50% state that this affects daily activity. There are few data on the nature of the symptoms these patients develop. This study aims to describe the symptoms troubling patients referred to a specialist Pelvic Radiation Disease clinic. Methods A prospective service evaluation of patients treated with pelvic radiotherapy referred to our clinic was performed. Patient characteristics were recorded. Each new patient completed a modified Gastrointestinal Symptom Rating Scale and Bristol Stool Chart which described their symptoms and severity. Results Data on the first 110 patients collected included 47 women (43%), median age, 59 (range: 37-79 years) and 63 men (57%) median age, 72 years (range: 20-83 years) treated for prostate (47%), gynaecological (27%) or anorectal cancers (17%), lymphoma (5%) and other tumours (4%). The median length of time since starting radiotherapy to presenting in clinic was 3 years 1 month; range: 0.5-36 years. Pelvic symptoms causing frequent or severe impact on patients daily lives were urgency (68%), diarrhoea (defined as Bristol stool chart type 6 or 7) (62%), tenesmus (55%), fatigue (51%), rectal flatulence (51%), abdominal pain (45%), faecal leakage (43%), sexual concerns (35%), problems with urination (34%), bloating (34%), borborygmi (30%), woken at night to defaecate (28%), rectal bleeding (24%), belching (20%), heartburn (15%), steatorrhoea (13%), nausea and vomiting (10%).Women presented with a median of 12 symptoms (range: 2-17) out of a maximum of 17 recorded symptoms and men with a
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