TMPRSS2-ERG gene fusions have recently been reported to be present in a high proportion of human prostate cancers. In the current study, we show that great diversity exists in the precise structure of TMPRSS2-ERG hybrid transcripts found in human prostates. Fourteen distinct hybrid transcripts are characterized, each containing different combinations of sequences from the TMPRSS2 and ERG genes. The transcripts include two that are predicted to encode a normal full-length ERG protein, six that encode N-terminal truncated ERG proteins and one that encodes a TMPRSS2-ERG fusion protein. Interestingly, distinct patterns of hybrid transcripts were found in samples taken from separate regions of individual cancercontaining prostates, suggesting that TMPRSS2-ERG gene fusions may be arising independently in different regions of a single prostate.

A potential association between abnormal electromyographic activity-that is, decelerating bursts and complex repetitive discharges-of the urethral sphincter and difficulty in voiding was examined in 57 women with urinary retention. Abnormal electromyographic activity was found in 33. Ultrasonography of the ovaries in 22 of the 33 women showed that 14 had polycystic ovaries. Of the other eight women, two had had oophorectomies, one had shrunken ovaries and ovarian failure, and one had previously undergone oophorectomy and the other ovary could not be seen; in one neither ovary could be seen, and three had ovaries of normal appearance, although two of these women were taking the contraceptive pill. Thirteen of the group had endocrine symptoms and signs characteristic of the polycystic ovary syndrome. Videocystometrography in 17 ofthe women who were examined by ultrasonography showed low flow rates and high residual volumes of urine after micturition in 12 women who could void, the other five having chronic urinary retention.A speculative hypothesis for the observed association of impaired voiding, abnormal electromyographic activity of the urinary sphincter, and polycystic ovaries is advanced, based on the relative progesterone deficiency that characterises the polycystic ovary syndrome. Progesterone stabilises membranes, and its depletion might permit ephaptic transmission of impulses between muscle fibres in the muscle of the urethral sphincter, giving rise to the abnormal electromyographic activity. This may impair relaxation of the sphincter, resulting in low flow rates of urine, incomplete emptying of the bladder, and, finally, urinary retention. than normal ovaries (mean volume 5 8 ml (4 6 to 7 3)), with a highly echogenic and dense central stroma and numerous (>10) peripherally located cysts of 4-6 mm in diameter.5 When associated with hirsutism, greasy skin, obesity, menstrual irregularity, and infertility the polycystic ovary syndrome may be the diagnosis.6 This condition is associated with increased concentrations of circulating androgens and luteinising hormone (with normal concentrations of follicle stimulating hormone) and, in 30% of cases, hyperprolactinaemia7 and occurs in 25% of women with amenorrhoea and 90% of those with hirsutism.' Patients and methodsFifty seven women with difficulties in voiding were referred to the department of clinical neurophysiology at the Middlesex Hospital during 1982-8 for electromyography of the urethral sphincter. The indication was retention of urine or dysfunction of voiding. The referring doctors were aware of our interest in the electromyographic abnormality,' and patients were clearly selected.Each patient underwent electromyography of the urethral sphincter with a concentric needle electrode,9-" and abnormal electromyographic activity (that is, decelerating bursts and complex repetitive discharges) was found in 33. Pelvic ultrasonography was carried out in 22 of the 33 women (the other 11, who had been early subjects and as secondary referrals from long...

Radiotherapy dose escalation improves tumour control in prostate cancer but with increased toxicity. Boosting focal tumour only may allow dose escalation with acceptable toxicity. Intensity-modulated radiotherapy can deliver this, but visualization of the tumour remains limiting. CT or conventional MRI techniques are poor at localizing tumour, but dynamic contrast-enhanced MRI (DCE-MRI) may be superior. 18 patients with prostate cancer had T(2) weighted (T2W) and DCE-MRI prior to prostatectomy. The prostate was sectioned meticulously so as to achieve accurate correlation between imaging and pathology. The accuracy of DCE-MRI for cancer detection was calculated by a pixel-by-pixel correlation of quantitative DCE-MRI parameter maps and pathology. In addition, a radiologist interpreted the DCE-MRI and T2W images. The location of tumour on imaging was compared with histology, and the accuracy of DCE-MRI and T2W images was then compared. Pixel-by-pixel comparison of quantitative parameter maps showed a significant difference between the benign peripheral zone and tumour for the parameters K(trans), v(e) and k(ep). Calculation of areas under the receiver operating characteristic curve showed that the pharmacokinetic parameters were only "fair" discriminators between cancer and benign gland. Interpretation of DCE-MRI and T2W images by a radiologist showed DCE-MRI to be more sensitive than T2W images for tumour localization (50% vs 21%; p = 0.006) and similarly specific (85% vs 81%; p = 0.593). The superior sensitivity of DCE-MRI compared with T2W images, together with its high specificity, is arguably sufficient for its use in guiding radiotherapy boosts in prostate cancer.

Doxazosin was well-tolerated and produced both urodynamic and symptomatic improvement in men with BPH, thereby providing a satisfactory alternative to existing drugs with the additional benefit of once daily dosage.

OBJECTIVES To investigate the relationship between prostate‐specific antigen (PSA) level and tumour volume for incidental adenocarcinoma of the prostate found in cystoprostatectomy (CP) specimens, and to analyse the incidence of clinically significant prostate cancers in CP specimens and the biochemical recurrence of incidental prostate cancers on short‐term follow up. PATIENTS AND METHODS Complete data from 97 of 105 prostates from CP specimens were available. Prostates were thoroughly analysed and sectioned at 2 mm intervals. PSA levels and the findings at digital rectal examination before surgery were obtained prospectively. None of the patients had any evidence of prostate cancer before CP. RESULTS Incidental prostate cancer was detected in 58 of 97 (60%) of the CP specimens; of these, 31 (53%) were significant according to the definition of Stamey et al. There was a weak correlation between tumour volume and PSA level, weighted solely by the four larger‐volume cancers. The median PSA level for patients with and without prostate cancer was not significantly different (3.1 vs 1.1 ng/mL, P = 0.06). The follow‐up of the 35 patients alive with prostate cancer showed four PSA recurrences (PSA >0.02 ng/mL) with one distant metastasis after a median follow‐up of 3 years. None of the patients with insignificant tumours developed biochemical recurrence. CONCLUSIONS The weak correlation between PSA level and tumour volume in these patients supports the argument that PSA is largely produced by benign prostatic hyperplasia and is therefore a poor screening tool for asymptomatic healthy men. Most incidental prostate cancers in CP specimens are significant, contrary to previous analyses, but have little practical importance in terms of oncological outcome.