No abstract

Germline mutations in the fumarate hydratase gene at 1q43 predispose to dominantly inherited skin and uterine leiomyomata and leiomyosarcomas. The enzyme, which is a component of the tricarboxylic acid cycle, acts as a tumour suppressor. To evaluate fumarate hydratase in respective sporadic tumours, we analysed a series of 26 leiomyosarcomas and 129 uterine leiomyomas (from 21 patients) for somatic mutations in fumarate hydratase and allelic imbalance around 1q43. None of the 26 leiomyosarcomas harboured somatic mutations in fumarate hydratase. Fifty per cent of leiomysarcomas tested showed evidence of allelic imbalance at 1q, but this was not confined to the vicinity of fumarate hydratase. Only 5% (seven out of 129) of the leiomyomas showed allele imbalance at 1q42-q43 and no somatic mutations in fumarate hydratase were observed. Our findings indicate that mutations in fumarate hydratase do not play a major role in the development of sporadic leiomyosarcomas or uterine leiomyomas.

Immunocytochemistry using a specific monoclonal antibody 9A7,y was used to identify receptors for calcitriol (1,25 (OH) Little is known of the cellular localisation of vitamin D receptors or vitamin D regulated proteins in the human intestine, or of the effects of disease on vitamin D regulated functions. Such studies might provide insight into the mechanisms by which vitamin D influences calcium absorption. In gluten induced enteropathy (coeliac disease) mucosal damage resulting in villous atrophy is most noticeable in the proximal small bowel, as the duodenum and jejunum bear the brunt of the enteropathy induced by ingested gluten. Calcium malabsorption with hypocalcaemia, osteopenia, and fractures are well recognised features.6 7 We have used immunocytochemical methods to examine whether changes in the distribution of vitamin D receptors and a calcium regulated protein (alkaline phosphatase) occurred in villous atrophy seen in patients with coeliac disease. As calcium absorption declines after the menopause, we were also interested to look for the presence of oestrogen receptors in duodenal mucosa. Methods BIOPSY SPECIMENSDistal duodenal biopsy specimens were obtained at endoscopy from eight patients with gluten induced enteropathy. Four untreated patients showed severe (3) and moderate (1) mucosal damage. Only one of four patients who had received a gluten free diet had a normal mucosa. The others showed persisting severe (2) or mild (1)

Colorectal cancer development is associated with a shift in host immunity with suppression of the cell-mediated immune system (CMI) and a predominance of humoral immunity (HI). Tumour progression is also associated with increased rates of cell proliferation and apoptosis. The aim of this study was to investigate whether these factors correlate and have an influence upon prognosis. Longterm follow-up was performed on 40 patients with colorectal cancer who had levels of tumour necrosis factor (TNF)-a, interferon (IFN)-g and interleukin (IL)-10 measured from stimulated blood cultures before surgery. Their archived tumour specimens were analysed to determine a Ki-67-derived proliferation index (PI) and a M30-derived apoptosis index (AI). Tumour necrosis factor-a levels negatively correlated to tumour proliferation (r ¼ À0.697, P ¼ 0.01). Interleukin-10 levels had a positive correlation with tumour proliferation (r ¼ 0.452, P ¼ 0.05) and apoptosis (r ¼ 0.587, P ¼ 0.01). Patient survival correlates to tumour pathological stage (P ¼ 0.0038) and vascular invasion (P ¼ 0.0014). An AIp0.6% and TNF-a levels X8148 pg ml À1 correlate to improved survival (P ¼ 0.032, P ¼ 0.021). Tumour proliferation and apoptosis correlate to progressive suppression of the CMI-associated cytokine TNFa and to and higher levels of IL-10. Survival is dependent upon the histological stage of the tumour, vascular invasion, rates of apoptosis and proliferation and systemic immunity which are all interconnected.