Serum IGF-1 determination in relation to prostate cancer screening: possible differential diagnosis in relation to PSA assays.
Prostate Cancer and Prostatic Diseases (2000) 3, 173-175
Biomedical subjects
Publications and source records attributed to W B Peeling.
Prostate Cancer and Prostatic Diseases (2000) 3, 173-175
As high grade PIN is commonly associated with concomitant cancer, current literature recommends re-biopsy of patients with high grade PIN. This paper describes the prevalence of high grade prostatic intra-epithelial neoplasia (PIN) from three independent clinical settings, reported by a single pathologist (MCP). High grade PIN was diagnosed in biopsies from 131 of the 1205 (11%) of patients in whom cancer was suspected in hospital practice, 42 of the 202 (20%) asymptomatic men screened for prostate cancer and 29 of the 118 (25%) patients presenting with prostatism in a case finding study. Re-biopsy on this scale has major clinical and cost implications. However, from a literature review, there is evidence to suggest that the risk of concomitant cancer with high grade PIN may be stratified according to serum PSA. This opinion should be tested prospectively.
OBJECTIVE: To determine the completeness of transurethral resection of the prostate (TURP). PATIENTS AND METHODS: The prostate volume of 432 patients was measured by transrectal ultrasonography (TRUS) before they underwent a TURP performed by one of three consultant urological surgeons. The prostate tissue collected at resection was weighed, multiplied by 1.2 to compensate for 'shrinkage', and the amount of tissue removed expressed as a percentage of the pre-operative prostate volume determined by TRUS (resection ratio). The patients were categorized into groups based on pre-operative prostate size. RESULTS: The mean weight of prostate tissue resected was 25.6 g. Resection ratios increased with prostate size, with the largest occurring in prostates of 71-110 g. The surgeon did not resect more than 50% of the gland volume in any group. CONCLUSION: This study counters the theory that a complete resection of the prostate is routinely achieved. The endoscopic appearances probably imply a complete resection of the adenoma but a considerable volume of the gland remains. This has important implications for the detection of prostate carcinoma at TURP and for the staging of the disease.
Epidermal growth factor receptor (EGFR) expression in 44 benign prostatic hyperplasia (BPH) and 55 prostatic carcinoma specimens has been investigated using Northern blot analysis and immunohistochemistry. The values obtained for the EGFR mRNA in the BPH and carcinoma specimens were not significantly different and in the latter there was no correlation with grade. In the immunohistochemical assays, two antibodies to the external and one to the internal domain of EGFR were used. The former ones stained the basal cell membranes intensely whilst cytoplasmic staining of secretory epithelium was seen in BPH specimens with the latter. In the carcinoma specimens, the intensity of membrane staining correlated with the two external domain antibodies, r = 0.640, P < 0.001, but neither of these correlated with the EGFR mRNA results. All three antibodies demonstrated a trend towards elevated expression of EGFR with dedifferentiation which reached significance only with the internal domain antibody results, P < 0.02. No correlation was observed with tumour EGFR mRNA values and the EGFR immunohistochemical results. The EGFR immunoreaction with the external domain antibody in 14 treated high-grade tumours was comparable to that obtained in 15 untreated anaplastic prostatic tumours. In 5 patients, both pre- and post-treatment samples were available and these exhibited little or no difference in EGFR expression with therapy.
The prostate gland has attracted a remarkable increase in interest in the past few years. The two most common diseases of this gland, benign prostatic hyperplasia and carcinoma of the prostate, have been brought into greater prominence by new diagnostic methods, public interest, and a wider choice of surgical and non-surgical treatments. Uncertainty about the significance of these changes has occurred because of the rapidity of change, the profusion of statements, opinions and promotions, and the relatively little guidance available from the profession. Ten urologists and two general practitioners have reviewed the relevant evidence about these two prostate diseases and the newer diagnostic methods; their conclusions are summarised here. Management options and guidance on clinical practice are also discussed. Because of a number of unresolved diagnostic and management issues, detailed requirements for practice guidelines have not been specified.
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Transforming growth factor alpha (TGF alpha) expression was analyzed immunocytochemically on formalin-fixed wax-embedded sections obtained from 24 benign prostatic hyperplasia (BPH) specimens and 76 prostatic carcinoma tissues, 3 human prostatic tumor xenografts, normal kidney, and salivary gland. Low amounts of TGF alpha immunopositivity were encountered in the epithelium of BPH glandular tissues, whereas in the prostatic adenocarcinoma samples, a greater heterogeneity and intensity of TGF alpha immunostaining was observed. The most intense staining was exhibited by the least differentiated tumors, although a few of these were weakly stained. Statistical analysis of the relationship of histopathological grade of tumor with TGF alpha expression in the carcinomas showed a significant correlation of these parameters, 0.01 > P > 0.001. The expression of the proliferation markers Ki-67 and PCNA was also analyzed in the carcinoma specimens, and the relationship of these to TGF alpha expression indicated that there was no significant correlation in this series of tumors between increased growth activity and TGF alpha expression (p approximately 0.25 with both markers). The prostatic carcinoma xenografts TEN12 and TEN15 contained low levels of immunoreactive TGF alpha, which was uniformly distributed, whilst heterogeneous immunostaining was observed in the uroepithelial xenograft TEN16. In the normal human kidney, TGF alpha was concentrated in the epithelium of the distal convoluted tubules (DCT) and the collecting tubules (CT), and lower amounts were identified in the proximal convoluted tubules (PCT). As in the prostatic carcinomas, the immunostaining was eliminated by prior absorption of the antibody with pure TGF alpha and not with human or mouse EGF. No crossreactivity of the TGF alpha antibody with salivary EGF was demonstrated. This study concludes that, in prostate carcinoma, the least differentiated tumors more often expressed greater amounts immunoreactive TGF alpha; however, no relationship between TGF alpha expression and cellular proliferation markers was found.
Granulomatous prostatitis is an unusual, but well-recognized entity frequently mistaken for carcinoma on both digital rectal examination and transrectal ultrasound. The ultrasonographic findings of 11 patients with histologically-proven granulomatous prostatitis are reviewed.
The side effects and patient acceptability of 230 ultrasound guided prostatic needle biopsies performed by the transrectal route in an out-patient setting were reviewed retrospectively. Most of the side effects were transient and mild; one patient required hospitalization for urinary retention. Patient acceptability was good; over 70% of patients reported no significant pain from the biopsy procedure.
The histological and transrectal ultrasound (TRUS) appearances at corresponding sites of the periphery of the prostate gland have been compared in 30 benign and 27 malignant glands taken at autopsy. In the benign series, the histological capsule was frequently absent and correlated poorly with the consistent TRUS findings of a regular, well-defined 'ultrasonic capsule'. It is concluded that 'the capsule' should be replaced as a tumour-staging landmark by a more realistic terminology. Carcinoma may be described as intra- or extra-prostatic, or confined or unconfined with respect to the gland. In the malignant glands, there was no correlation between morphologically unconfined cancers and irregular or absent ultrasound 'capsule' when corresponding areas were compared. This disparity must contribute to an underestimation of tumour extent with TRUS.
Proliferating cell nuclear antigen (PCNA) expression was determined immunohistochemically, using a monoclonal antibody PC10, in 102 prostatic carcinoma samples and in prostate tissue from 21 patients with benign prostatic hyperplasis (BPH). The percentage of cells with stained nuclei ranged from 1% to 58% in the carcinoma specimens and 0% to 10% in the BPH specimens. A semiquantitative scoring system was devised for the degree of PCNA positivity observed in the tumors. Statistical analysis of the PCNA score in relation to the histological grade of the tumors gave a significant positive or negative correlation between these parameters P less than 0.001. No significant correlation between PCNA score was, however, seen with metastatic status, T category (TMN classification) of the primary tumor, or the patient's age at diagnosis. In 65 prostatic cancer patients of known survival, those individuals whose tumors had a PCNA score of +/- (less than 10% of nuclei stained) were compared with those patients whose tumors were either 1+, 2+, or 3+ (greater than 10% of nuclei stained). Life table analysis of the two groups indicated that the patients with the lower PCNA score survived significantly longer than those with the higher PCNA scores, P less than 0.04. Comparison of the Ki-67 expression in frozen sections with the PCNA expression in wax-embedded tissue of 86 prostatic carcinomas was also undertaken. A significant correlation between these two parameters was found, P less than 0.001, although the growth fraction estimated by Ki-67 expression was generally lower than that given by the PCNA scoring system.
Estimation of the growth fraction of 153 prostatic carcinoma specimens employing Ki-67 immunostaining was undertaken and its relationship to various clinical parameters investigated. In prostate specimens, the percentage of tumour nuclei expressing Ki-67 antigen was measured and assigned a Ki-67 score. It was observed that high Ki-67 scores were associated with the poorly differentiated tumours, the correlation of this proliferation marker with histological grade was found to be significant (P less than 0.001). No relationship was observed between the Ki-67 score of the primary tumour with either the patient's age or with the primary tumor stage (T category). The metastatic status of the patient at diagnosis and the Ki-67 score of the tumour were correlated (P less than 0.05), higher Ki-67 scores being associated with M1 disease. Life-table analysis of 86 patients who subsequently received androgen withdrawal therapy, was undertaken with reference to the various Ki-67 scores of their primary tumors. A statistically significant difference in survival times was observed in patients whose Ki-67 values were less than 1% (P less than 0.0001) when compared to those patients whose tumours expressed 1% and over Ki-67 positivity, the former having longer survival times. When patients were subdivided according to their metastatic status and similar life-table analyses were carried out, no statistical difference was found between survival times and Ki-67 scores in M0 staged patients. In the M1 population of patients, however, those patients whose tumours were negative for Ki-67 expression had significantly longer survival times than those patients whose tumours exhibited positive Ki-67 staining (P less than 0.01). Comparing M1 staged patients whose prostate tumor cells exhibited less than 1% Ki-67 positive nuclei with M1 staged patients whose prostate tumour cells contained 1% and higher Ki-67 stained nuclei, a significantly longer survival time was found in the former group of patients (P approximately 0.0001).
This retrospective study correlated prostate volume, determined by transrectal ultrasonography, with serum prostate specific antigen (PSA), by Deming regression analysis, in patients with confirmed benign prostatic hyperplasia (BPH) and patients with non-metastatic (M0) or metastatic (M1) prostate cancer. In BPH, a highly significant correlation was found between log10[PSA] and prostate volume. When this PSA/volume regression pattern for BPH was used as a reference standard, all 17 patients with M1 prostate cancer and 83% of the 23 patients with M0 disease were discriminated from BPH.
Seminal vesicle cysts may arise from inflammation or obstruction of the seminal vesicle or from embryological remnants such as the müllerian duct. Surgical removal has been proposed as the treatment of choice. A 19-year-old boy presented with abdominal pain and constipation. Investigations revealed a 14-cm multiloculated cyst arising from the right seminal vesicle and a small stone lodged at the orifice of the ipsilateral ejaculatory duct. Following endoscopic removal of the stone the mass decreased in size considerably and 2 months later transrectal ultrasound and magnetic resonance imaging showed normal seminal vesicles and no evidence of the cyst. This case strongly supports an obstructive aetiology for this cyst and we would suggest that, in similar cases, full assessment of the ejaculatory apparatus should be carried out to exclude an obstructive cause before embarking on major surgery.
Serum prostatic specific antigen (PSA) and ultrasound-determined prostatic volume (UPV) were measured in 50 patients with histologically proven benign prostatic hyperplasia (BPH) and in 40 patients with histologically proven prostatic cancer of whom 17 had evidence of distant metastases (M1) and 23 did not (M0). A good correlation between log PSA and UPV was demonstrated in the BPH group and rearrangement of the linear regression equation allowed calculation of a single variable--the log PSA corrected to a standard prostate volume for any given individual. A volume-corrected PSA correctly identified all patients with M1 disease and greatly improved but did not eliminate overlap of M0 disease with BPH. Reduction of serum PSA to a single volume-corrected variable will allow the introduction of practical and optimum protocols for the management of patients with prostatic enlargement.