Effects of finasteride on the vascular surface density, number of microvessels and vascular endothelial growth factor expression of the rat prostate.

INTRODUCTION: Finasteride is a 5-alpha-reductase inhibitor used in the medical treatment of benign prostatic hyperplasia (BPH) and appears to be effective in treating prostatic bleeding secondary to BPH. The exact mechanism of this effect is not known. The aim of this study was to evaluate the effects of finasteride on the vascular surface density (VSD), number of microvessels (NVES) and vascular endothelial growth factor (VEGF) expression of the rat prostate. MATERIALS AND METHODS: Nineteen adult male rats were used. Finasteride was given to 14, and there were 5 in the control group. Finasteride 80 mg/kg was administered daily via orogastric tube as a suspension for three months. Rats were sacrificed and vascular structures of the prostates were labelled immunohistochemically using CD31 antibodies. VSD and NVES of the prostates were assessed by means of a peroxidase labeled streptavidin-biotin method. VEGF expression was examined by immunohistochemistry using VEGF monoclonal antibody. RESULTS: Mean prostatic weights were decreased significantly in rats given finasteride (p=0.0001). Although an increase in VSD was detected in the finasteride group it was not significant (p=0.26). NVES was significantly increased in the finasteride group (p=0.033). No significant difference was detected between the two groups in terms of VEGF expression (p=0.48). CONCLUSION: Finasteride does not seem to decrease VSD, NVES and VEGF expression at the level of the rat prostate. The effect of reduction of bleeding in BPH is likely to be due to its effect on shrinking glandular hyperplasia which might enhance vessel wall stability rather than decreasing overall vascularity.

Association of mast cells with microvessel density in renal cell carcinomas.

BACKGROUND: Growth of solid tumors requires angiogenesis. Evidence indicates that mast cells (MCs) play an important role in tumor angiogenesis. The aim of this study was to investigate the possible effects of angiogenesis and the presence of MCs on the prognosis of renal cell carcinoma (RCC). METHODS: Seventy-one patients who underwent radical nephrectomy for RCC were included in this study. Paraffin sections from tumor and nonneoplastic kidney were stained with CD31 antibody with the standard streptavidin-biotin immunperoxidase method. Microvessels were quantified by a stereologic method. Tumors and the surrounding area were also stained with toludine blue stain to show MCs in tumor and surrounding tissue. The correlation between microvessels and MC counts was evaluated and compared with tumor stage, grade, and other clinicopathologic parameters. RESULTS: MCs in RCC and peritumoral areas were observed to be greater than nonneoplastic kidney tissue. No correlation was found between MC number and various clinicopathologic features such as tumor size, stage, grade, and patient survival. No association was noted between angiogenesis and clinicopathologic features. On the other hand, significant correlation was found between the number of MCs and microvessel density (p=0.034, r=0.295). CONCLUSION: Our results suggest that MC infiltration may contribute to tumor angiogenesis and acceleration of tumor growth, whereas stereologic assessment of angiogenesis does not help to predict biologic behavior in RCC. Further research is required to confirm these observations.

Expression of COX-2 in normal and pyelonephritic kidney, renal intraepithelial neoplasia, and renal cell carcinoma.

OBJECTIVES: The role of inflammation in carcinogenesis is unknown. To determine the relationship between cyclooxygenase 2 (COX-2) expression, inflammation, and carcinogenesis in human renal cell carcinoma (RCC), we looked for COX-2 expression in normal and pyelonephritic kidney, renal intratubular neoplasia (RIN), and RCC tissues. METHODS: COX-2 expression was assessed immunohistochemically in tissues obtained from 20 pyelonephritic kidneys, 16 normal kidneys, 19 RIN, and 75 RCC cases. RESULTS: COX-2 expression was found to be positive in 64% of RCCs. It was positive in 13 chronic pyelonephritic (65%), 9 normal (56%), and 15 RIN (79%) cases. COX-2 expression was significantly higher in RCC and RIN than the normal and pyelonephritic cases (p<0.001 and p<0.001, respectively). No statistically significant difference was noted between RCC and RIN cases. CONCLUSIONS: Although the function of COX-2 in tumor development has not been exactly elucidated, the increased expression of COX-2 in RIN and RCC might be a factor that may play a role in the development of RIN or progression to RCC, which warrants further research.

Risk factors for mucosal prostatic urethral involvement in superficial transitional cell carcinoma of the bladder.

OBJECTIVE: Prostatic transitional cell carcinoma (TCC) may involve urethral mucosa, ducts, acini and stroma of the gland. In this study, we evaluated the risk factors for mucosal prostatic urethral (PU) involvement in superficial TCC of the bladder. METHODS: The data of 340 consecutive male patients with the diagnosis of primary superficial TCC of the bladder who were treated at our institution were reviewed. Median age of the patients was 64 years and median follow-up was 66 months. The impact of pathological stage, grade, tumour multiplicity and presence of carcinoma in situ (CIS) on mucosal PU involvement were evaluated. RESULTS: Twenty one patients (6.2%) had mucosal involvement of the PU and concomitant multifocal TCC of the bladder. Of those, 12 patients (3.5%) had macroscopic mucosal involvement of the PU while the other 9 patients (2.7%) had microscopic tumour. Increased pathological stage, grade and tumour multiplicity were found to be risk factors for mucosal PU involvement in patients with superficial bladder cancer. Multivariate analysis showed that only the tumour multiplicity was found to be an independent risk factor for mucosal PU involvement by TCC (p=0.001). CONCLUSIONS: The incidence of mucosal PU involvement increases as the stage, grade and number of tumours increase in patients with superficial TCC of the bladder. We recommend PU sampling particularly in patients with multiple bladder tumours which may have an impact on further management of these patients.

1,25 Dihydroxyvitamin D(3) receptor expression in superficial transitional cell carcinoma of the bladder: a possible prognostic factor?

OBJECTIVE: Vitamin D receptors (VDR) have been detected in normal tissues and in a number of cancer types. This study was undertaken to determine the VDR expression status and to elucidate the prognostic significance of VDRs in superficial transitional cell carcinoma (TCC) of the human bladder. METHODS: VDR expression was investigated in the tumour tissue blocks which were obtained by transurethral resection from 105 patients with superficial TCC without concomitant carcinoma in situ and in 30 control subjects. Median follow-up of the patients was 40 months. The expression of nuclear VDR was evaluated immunohistochemically using avidin-biotin-peroxidase method and a monoclonal VDR antibody. VDR staining intensity in samples were assessed semi-quantitatively and graded as [-] if VDR was lacking, [+] if <33% of cells were stained, [++] if 33-66% of cells and [+++] if >66% were stained. Staining characteristics were compared with the clinico-pathologic results. RESULTS: VDRs were detected in 85.7% of the patients with superficial TCC and in 66.6% of the controls (p = 0.02). No correlation was found between VDR expression and pathological stage and grade (p = 0.05 and p = 0.09, respectively). Progression in pathologic stage was significantly higher in VDR[+++] tumours (p = 0.001). Also, disease-free survival was significantly lower and tumour size was significantly greater in VDR [+++] tumours than [-], [+] and [++] ones (p = 0.02, p = 0.008 and 0.007, respectively). No significant difference was found between patient age, sex, tumour multiplicity in terms of VDR expression. Survival was not affected by VDR expression. In multivariate analysis VDR expression was not found to be an independent prognostic factor. CONCLUSION: Superficial TCC of the bladder express VDRs. The association of increased VDR expression and higher disease progression may be useful in discriminating less differentiated superficial TCCs with poor outcome.

Conservative management of mucosal prostatic urethral involvement in patients with superficial transitional cell carcinoma of the bladder.

OBJECTIVE: Treatment of patients with mucosal prostatic urethral transitional cell carcinoma (TCC) is controversial. In this study, we evaluated the outcome of patients with mucosal prostatic urethral TCC who were managed conservatively. METHODS: The data of 290 consecutive male patients with superficial TCC of the bladder who were treated at our institution were reviewed. Median age was 63 years and median follow-up was 63 months. Initially, all patients with mucosal PU involvement without evidence of ductal and/or stromal involvement underwent intravesical BCG or Epirubicin therapy. RESULTS: Nineteen patients (6.6%) had mucosal involvement of the prostatic urethra (PU) and concomitant multifocal TCC of the bladder. Of those, 12 patients (12/19, 4.2%) had macroscopic mucosal involvement of the PU, while the other 7 patients (7/19, 2.4%) had microscopic PU tumor. Seven of 12 patients who were treated with BCG and 2 of 7 patients who were treated with Epirubicin achieved complete response. Progression occurred in 3 patients who received BCG and no patients progressed in the Epirubicin group. CONCLUSIONS: Prostatic urethral sampling should be considered necessary in intermediate and high risk patients with superficial TCC of the bladder. Intravesical therapy, especially with BCG seems to be an effective treatment alternative in the management of mucosal PU involvement.

Primary renal lymphoma of mucosa-associated lymphoid tissue.

Mucosa-associated lymphoid tissue-type lymphomas have recently been recognized as a distinctive form of B-cell malignant lymphoma. In contrast to other types of low-grade lymphomas, these tumors have a tendency to be localized at diagnosis and to be curable with local therapy. We report an unusual case of primary localized low-grade lymphoma of mucosa-associated lymphoid tissue arising in the kidney. The patient underwent radical nephrectomy and was free of disease at 28 months of follow-up without additional treatment. Once properly staged and classified, lymphoma of mucosa-associated lymphoid tissue involving the kidney can be managed by radical nephrectomy and follow-up.

Prognostic significance of estrogen receptor expression in superficial transitional cell carcinoma of the urinary bladder.

OBJECTIVES: The role of estrogens in human bladder cancer still remains to be resolved. This study was undertaken to determine the estrogen receptor (ER) expression status and to elucidate the prognostic significance of ER in superficial transitional cell carcinoma (TCC) of the human bladder. METHODS: Tumor tissue blocks which were obtained by transurethral resection (TUR) from 121 patients with superficial TCC and 30 control subjects were investigated. Median follow-up was 40 months. The expression of nuclear ER was evaluated by immunohistochemistry using avidin-biotin-peroxidase method and a monoclonal ER antibody. ER staining intensity in samples was assessed semi-quantitatively. Staining characteristics were compared with the clinico-pathological results. RESULTS: ERs were detected in 12.4% of the superficial TCC patients and in 10% of the controls (P = 0.73). No association was found between ER immuno-reactive score and patients' age, sex, tumor multiplicity or tumor size. An association between the ER staining intensity and higher tumor grade was observed (P = 0.01). Grades I, II and III tumors showed 10.6, 8.7 and 44.4% staining, respectively. Survival was not affected by ER expression. In multivariate analysis ER expression was not an independent prognostic factor. CONCLUSION: Superficial TCC of the bladder shows low ER expression and it appears that ERs do not have any direct role on the prognosis of patients with superficial TCC.