Predictive value of cyclooxygenase-2 over expression for identifying prostate cancer from benign prostatic hyperplasia in prostate biopsy specimens.

BACKGROUND: We studied cyclooxygenase-2 (COX-2) immunohistochemical staining intensity both in prostatic biopsy and surgical samples of patients with prostate cancer to determine if it might provide prognostic information for the decision of re-biopsy indication. METHODS: Twenty-eight patients undergone radical prostatectomy whose final pathologic examination revealed prostatic adenocarcinoma were included in the study. Twelve patients with BPH in their pathological examination of both prostatic biopsy and open prostatectomy were considered as a control group. Intensity of COX-2 receptor was examined with immunohistochemical staining according to standard techniques. RESULTS: Positive COX-2 receptor staining was obtained 89.3% of biopsy samples and 93% of surgical samples in all cancer patients. The rate of agreement in COX-2 receptor staining of biopsy samples and radical prostatectomy samples was 76% in same patients (P=0.54). Similarly, the COX-2 receptor levels in biopsy specimens of patients with BPH open surgery compared with samples of the agreement still rate was 41% (P=0.41). Prostate cancer exchanging COX-2 receptor levels in patients with biopsy specimens in patients with BPH were found significantly more (P=0.008). CONCLUSIONS: In this study the feasibility of presence of COX-2 receptor staining in biopsy samples was shown. We have also demonstrated that COX-2 staining intensity was higher in prostatic biopsy samples of patients with prostatic cancer than patients with BPH. This leads a conclusion that, higher COX-2 expression levels in biopsy specimens may be used to decide re-biopsy in borderline preoperative PSA levels as well as in the cases with suspicious pathological findings for cancer.

Selenium, nickel, and calcium levels in cancerous and non-cancerous prostate tissue samples and their relation with some parameters.

In the present study, tissue samples of patients with cancerous and non-cancerous prostate were analyzed for their Se, Ni, and Ca contents. Possible relationship between Se, Ni, and Ca concentrations and some parameters including preoperative prostate-specific antigen (PSA) levels, histopathological neurovascular invasion, extra-capsular extension, seminal vesicle invasion, positive surgical margins, PSA relapse after radical prostatectomy, and total Gleason scores were obtained. Inductively coupled plasma (ICP) optical emission spectrometry and ICP-mass spectrometry instruments were used for the determination of analytes interested. All the system parameters in digestion and measurement steps were optimized to obtain efficient digestion and sensitive measurements. There was no statistically meaningful difference observed in the concentration of selenium in cancerous and benign prostatic tissues (p = 0.347) while nickel levels in cancerous tissues were observed as significantly lower than benign tissues (p < 0.001). In addition, calcium concentration in cancerous tissue samples were found to be statistically lower than those in benign tissues (p < 0.001) with mean values of 657 and 1,431 mg/kg, respectively.

Possible relations between oxidative damage and apoptosis in benign prostate hyperplasia and prostate cancer patients.

Cancer has been described as the twentieth century plague, and is a very common health problem. It has been reported that ROS and ROS products play a key role in cancer and that oxidative damage is effective in apoptosis initiation. In this study we aimed to evaluate the relationship between MDA (malondialdehyde), DNA damage (8-hydroxyguanine, 8-OH-dG), and caspase-3 in BHP and prostate cancer patients. Twenty male patients with prostate cancer and 20 male patients with benign prostate hyperplasia were included into this study. The MDA (nanomole), DNA damage (nanograms per millilitre), and caspase-3 (nanograms per millilitre) levels were measured in prostate cancer and benign prostate hyperplasia using Elisa kits (Millipore Corporation, Billerica, MA, USA). In the prostate cancer group, serum MDA (30.96 ± 9.25) and DNA damage (4.42 ± 0.36) levels were significantly raised (p < 0.05) when compared to the benign prostate hyperplasia group (24.05 ± 8.06, 3.99 ± 0.54). However, in the prostate cancer group, serum caspase-3 (2.36 ± 0.82) levels were statistically significantly lowered (p < 0.05) compared with the benign prostate hyperplasia group (3.15 ± 1.04). We observed that altered prooxidant, DNA damage levels may lead to an increase in oxidative damage and may consequently play an important role in prostate carcinogenesis. These findings indicate that, although the triggering of these changes is unknown, changes in the levels of MDA, DNA damage, and caspase-3 in the blood are related to prostatic carcinoma development. In addition, it would be appropriate to conduct new studies with a large number of patients at different stages.

Prevalence of prostate cancer in high boron-exposed population: a community-based study.

We investigated the possible relationship between boron exposure and prostate cancer (PCa) for men living and being employed at boron mines in villages with rich boron minerals. Out of 456 men studied, 159 were from villages with rich boron sources and boron levels in drinking water of >1 mg L(-1) and these men formed the study group, while 63 from villages with rich boron sources and boron levels in drinking water of <1 mg L(-1) were enrolled into control group 1. A further 234 subjects from other villages with no boron mines were considered as control group 2. Prostate specific antigen (PSA) levels could be obtained from a total of 423 men. Urinary boron concentration as an indicator of boron exposure in 63 subjects, prostatic volumes by transrectal ultrasonography in 39 subjects, and prostatic biopsies in 36 subjects were obtained for study and control groups. The daily boron exposure was calculated according to urinary boron levels. Although there was no significant difference among the groups in terms of total PSA levels, the number of subjects with tPSA ≥2.5 and tPSA ≥10.0 ng dL(-1) prostatic volumes in men whose prostates were biopsied (p < 0.012) was significantly lower in the study group as compared with those in the control group 2. These results suggested that high exposure to boron might have an implication within the prostatic cellular processes related to hyperplasia and carcinogenesis, even though we did not find a statistically significant association between PCa and boron exposure.

Effects of chronic boron exposure on semen profile.

The possible changes in semen quality were studied in men living in a boron mining area. The subjects in the boron group had exposure to boron at an average level of 6.5 mg/day, as determined by urinary analysis. The results obtained by the boron group were compared to those obtained for the control group whose subjects were living in the same geographical area but away from the boron region; average exposure level was 1.4 mg/day for this group. The semen samples were analyzed according to the recommendations of the World Health Organization. Boron levels were established in the water samples obtained from various locations in the study region. In the boron mining fields where the subjects in the boron group live, water samples contained boron in the range of 1.4-6.5 mg/L, while the values were <0.01 mg/L for the water samples obtained from the region where the subjects of the control group reside. No negative effects were found in the sperm samples obtained from the subjects of the boron group.

Sorafenib in metastatic renal cell carcinoma with sarcomatoid differentiation.

Targeted therapy in the management of metastatic renal cell cancer has been recently introduced to urology practice. The drugs used for management are used in a very limited number of patients and only for clear cell histology. We present a case where we administered sorafenib, a multikinase inhibitor of tumor-cell proliferation and angiogenesis, to a patient with metastatic renal cell carcinoma of clear cell histology. We found that our results were different from those of previously reported studies, because sarcomatoid differentiation was evident in a histological examination of this case. There was an excellent response to sorafenib. This case report might provide evidence that antiangiogenic agents may be active in any histological type of renal cell carcinoma. However, there are no available data to demonstrate the duration of response and survival benefit.

Urachal urothelial carcinoma diagnosed at a radical prostatectomy operation: a case report.

BACKGROUND: Urachal carcinomas are rare tumors, and the majority of them are adenocarcinomas. Up to now, only 21 urachal urothelial carcinomas (UCas) have been reported. Here, we describe a case of high grade UCa arising from the urachal remnants. CASE: A 66-year-old man presented with voiding difficulties. Prostate specific antigen (PSA) was 5.46 ng/mL. Prostatic adenocarcinoma (PCa) (Gleason score 6) was diagnosed by needle biopsies. After the diagnosis of high grade, muscle invasive UCa with intact mucosa on frozen examination of the dome of bladder wall during the radical prostatectomy operation (RPO), partial cystectomy was performed. Microscopically, among the tumoral islands, cystic structures lined by cells with a benign appearance, which are considered urachal remnants, were noted. Cytokeratin 7 and high-molecular-weight cytokeratin were strongly positive, PSA and carcinoembryonic antigen were negative. Radiotherapy was given for both UCa and PCa. Six months after the diagnosis, an undifferentiated tumor was detected in a bladder transurethral resection specimen; thus, chemotherapy was given. After 1 course of chemotherapy, the patient was doing well. CONCLUSION: The origin of urachal carcinomas is usually obscured as it is a highly invasive carcinoma. The patient presented here was diagnosed incidentally during RPO. Although the stage was advanced, the tumor was detected before urachal remnants were destroyed. The treatment choice for urachal carcinomas is cystectomy. Adjuvant chemotherapy and radiotherapy are controversial.

Comparison of the desmoplastic reaction and invading ability in invasive ductal carcinoma of the breast and prostatic adenocarcinoma based on the expression of heat shock protein 47 and fascin.

OBJECTIVE: To investigate the diversity within invasive ductal carcinoma (IDC) and prostatic adenocarcinoma (PCa) by evaluating immunohistochemical expression of heat shock protein 47 (HSP47) and fascin, the molecules that are related to desmoplasia and invasion, and analyze its correlation with clinicopathologic parameters. STUDY DESIGN: HSP47 and fascin immunoreactivity (IR) was evaluated in 49 mastectomies diagnosed as IDC and 57 radical prostatectomies diagnosed as PCa. IR was evaluated as: 0: < 5%, 1+: 5-25%, 2+: 25-50%, 3+: > 50%. RESULTS: HSP47 and fascin were localized to cytoplasm, and HSP47 and fascin IR were higher in IDC and PCa than benign groups (p < 0.05). HSP47 IR in neoplastic cells was 42.1% and 28.6%, in stroma was 81.6% and 15.8% in IDC and PCa, respectively; fascin IR in neoplastic cells was 65.3% in IDC and 15.8% in PCa. Fascin expression correlated with estrogen receptor and progesterone receptor negativity, tumor size and stage in IDC and surgical margin status in PCa. HSP47 expression correlated bilaterality in PCa. HSP47 positively correlated with survival in IDC. CONCLUSION: HSP47 and fascin expression may play role in the pathogenesis of IDC and PCa because their expression is significantly higher in IDC and PCa than their normal counterpart. Although there is no relationship with recurrence or metastatic status, fascin overexpression correlated with tumor size, which may prompt its use as a prognostic factor in IDC.

Effects of neuronal and glial restricted precursor cells transplantation on erectile function after experimentally induced spinal cord injury.

INTRODUCTION: Erectile dysfunction is common among patients with spinal cord injury (SCI). AIM: This study aims to investigate the recovery of penile erectile functions of the rats with spinal cord injury (SCI) following transplantation of endogenous neuronal precursors cell (neuronal restricted precursors [NRP]/glial restricted precursors [GRP]) into the injured area of spinal cord. METHODS: Twenty-two rats were experimented in three groups. Group 1 (N = 6): Sham; Group 2 (N = 10): SCI + NRP/GRP transplanted in day 9 after operation; Group 3 (N = 6): SCI + culture medium transplanted in day 9 after operation. Analysis of penile reflexes and cavernosal nerve stimulation studies were performed in day 28 after transplantation for each group. All rats in three groups were then sacrificed and the injured regions of spinal cords underwent histological investigation. MAIN OUTCOME MEASURES: These results show improvements to some extent in locomotor and erectile functions although these improvements are far from full functional recovery. RESULTS: Cavernosal nerve stimulation resulted in significantly higher intracavernosal pressure in Group 3 (SCI) although there was no difference between Group 1 (sham) and Group 2 (SCI + NRP/GRP). Number of clusters was similar between groups. Number of erections was higher in Group 3 (SCI) than Groups 1 and 2, and number of cups was higher in Group 2 (SCI + NRP/GRP) than the other two groups. Number of flips was similar in Groups 1 and 2 but lower in Group 3. Number of long flips was highest in Group 1 and lowest in Group 3. The differences between groups were significant. CONCLUSION: This study emphasized the healing potential of NRP/GRP transplantation following experimental SCI. However, further experimental and clinical studies are required to advance this treatment modality.

Serum lipid levels in benign prostatic hyperplasia.

The relationship between serum lipid levels and measures of benign prostatic hyperplasia was investigated. The study was community based. All the participants had undergone a urological investigation which included International Prostate Symptom Score (I-PSS) and Quality of Life Score (QoL), serum lipid concentrations and determination of prostate volume with transrectal ultrasonography. Body mass index was calculated with the formula of weight (kg)/surface area (m(2)) respectively. Men were considered obese if their body mass index was over 25 kg/m(2). BPH was defined by prostate volume greater than 20 ml and I-PSS greater than seven. Comparisons of serum lipid levels between men with BPH and without BPH were done. There was no correlation for serum lipid levels with either mean I-PSS and QoL scores. However, triglyceride and cholesterol levels were the lowest in severe symptomatic men than men with low symptoms. Using clinical definition of BPH that prostate volume was greater than 20 ml and I-PSS was greater than seven, men with BPH had not significantly different serum lipid levels from men without BPH. Our population-based data reflect that there was no relationship between serum lipid levels and certain physiological measures of lower urinary tract symptoms and clinical benign prostatic hyperplasia.

Population standards of prostate specific antigen values in men over 40: community based study in Turkey.

OBJECTIVE: To determine the prostate specific antigen (PSA) population standards of a cluster of Turkish men with no clinical evidence of prostate cancer. PATIENTS AND METHODS: We evaluated PSA values of the men who were living in a well-defined, rural district of Western Anatolia. Two hundred fifty-seven men agreed to participate in this population-based study. They underwent clinical examination, transrectal ultrasonography and serum PSA measurement. The association between serum PSA and age, prostate volume and age, PSA and prostate volume, and PSA density (PSAD) and age were assessed. Distributions of serum PSA levels, prostate volumes (PV), and PSAD values as a function of age were generated. RESULTS: The upper limit of normal PSA concentration were 4.51 ng/ml for men aged 40-49 years, 4.36 ng/ml for 50-59 years, 6.17 ng/ml for 60-69 years, and 10.18 ng/ml for over 70 years. The upper limit of normal (95th percentile) for the serum PSA concentration increased with age. Across the entire age range, no correlation was found between the serum PSA concentrations and age while significant correlation was found between serum PSA concentration and prostate volume. CONCLUSION: In this present study, the PSA values in different age intervals showed higher than those observed in previous studies. The PSA values are mainly affected by prostate volume rather than age.

Evaluation of pain caused by urethrocystoscopy in patients with superficial bladder cancer: a perspective of quality of life.

AIM: The aim of this study is to evaluate patients' tolerance to pain caused by urethrocystoscopy (UCS) in both diagnosis and the period of follow-up in patients with superficial bladder cancer, and to evaluate these results with respect to quality of life. PATIENTS AND METHODS: Between March 2003 and October 2004, 66 patients with bladder cancer or hematuria underwent UCS and recorded their overall pain level. RESULTS: The mean age was 60.4 (range 26-83) years. UCS was done only one time in 22 patients for the diagnosis of etiology of hematuria and was done 4 times in 44 patients every 3 months for bladder cancer follow-up. The mean pain scores on first, second, third, and fourth UCS were 4.3+/-2.2, 4.7+/-2.5, 4.68+/-2.45, and 5.1+/-2.5, respectively. Statistically significant differences were found among mean pain scores of patients on first, third, and forth cystoscopic examinations (p < 0.05). No correlation was found between age and pain scores in this study group (p > 0.05). CONCLUSION: UCS is a painful surgical procedure and pain tolerance was not observed on repeated UCS. Therefore urologists need to use more effective anesthetic methods to provide better patients' tolerance to pain and quality of life during the endoscopic procedure.

Validation of 2001 Partin tables in Turkey: a multicenter study.

OBJECTIVE: Although Partin tables were developed in United States to predict the stage of prostate cancer preoperatively, they are used by many clinics throughout the world assuming that these figures apply to their population as well. However the predictive value of current Partin tables, which was updated in 2001, has not been validated in most of the countries as well as in Turkey. Therefore, we evaluated the validity of 2001 Partin tables, for the ability to predict the pathological stage in Turkish patients. PATIENTS AND METHODS: The clinical and pathological findings of 1043 patients who have had radical prostatectomy were assessed. Serum PSA values, clinical stage, biopsy Gleason score and the pathological features of the radical prostatectomy specimens were collected from each clinic and evaluated. The predictive value of Partin nomogram and pathological findings of prostatectomy specimens were compared and analyzed according to Receiver Operating Characteristics (ROC) analysis. RESULTS: Median age of the patients was 60 (45-74). In the presented study, percentage of patients with clinical stage T1c was 43%. Patients with Gleason score of 2-4 in biopsy constituted 23.4% of the study group. In the present study, the ratio of the patients with serum PSA higher than 10 ng/ml was 39.6%. Organ confined disease, seminal vesicle involvement, lymph node metastases ratios were 64.7%, 10.3%, 1.8% respectively. Area Under Curve (AUC) values for organ confined disease, seminal vesicle involvement and lymph node involvement were calculated as 0.665, 0.733 and 0.759 respectively. CONCLUSION: It appears that Partin tables have a reasonable predictive value for the final pathological features like organ confined disease, seminal vesicle and lymph node involvement in Turkish patients. This multicenter study showed that current Partin tables could also be used in Turkish patients with comparable accuracy.

Comparison of the nuclear matrix protein 22 with voided urine cytology in the diagnosis of transitional cell carcinoma of the bladder.

Several urinary markers for transitional cell carcinoma have been investigated, including urine cytology, bladder tumor antigen, autocrine motility factor receptor and fibrin degradation products. Unfortunately, they have poor overall sensitivity. The United States Food and Drug Administration have recently approved nuclear matrix protein (NMP 22) for the detection of occult or rapidly recurring disease after transurethral resection of bladder tumor. The objective of the current study was to assess the sensitivity of NMP 22 for the detection of bladder carcinoma, as well as to correlate the NMP 22 values with multiplicity of tumor, tumor size, configuration, stage and grade respectively. A total of 78 patients (38 with bladder cancer) provided a urine sample which was divided into appropriate aliquots for each of urine cytology and NMP 22. Comparative results demonstrate a clear superiority of NMP 22 in bladder cancer detection (52.6% vs 31.6% sensitivity), while specificity was in favor of urine cytology (100% vs 82.5%). For superficial tumors, sensitivity was 78.5% for NMP 22 and 41.6% for cytology and for invasive cancers, sensitivity was 90% for NMP 22 and 60% for cytology. Urinary NMP 22 levels were significantly correlated with tumor grade and were significantly higher in large tumors than small tumors. NMP 22 test results showed sufficient sensitivity in comparison with urine cytology for the detection of transitional cell carcinoma. However, we do not think that it is a useful tool as a substitute for endoscopic examination for the detection and surveillance in bladder cancer.

Bullous pemphigoid associated with prostate adenocarcinoma.

Bullous pemphigoid is a common autoimmune skin disease characterized by the presence of subepidermal blisters. It has been associated with underlying neoplasia in isolated reports. A 78-year-old man with generalized blisters was diagnosed as bullous pemphigoid on clinical, histopathological and direct immunofluorescence grounds. His free and total prostate specific antigen (PSA) levels were high and histopathological examination of a prostate specimen revealed prostate adenocarcinoma. We present this rare case to discuss the possible association between bullous pemphigoid and prostate adenocarcinoma.

Col IV and Fn distribution in prostatic adenocarcinoma and correlation of 67LR, MMP-9 and TIMP-1 expression with Gleason score.

OBJECTIVE: To assess the immunoreactivity of 5 proteins related to basement membrane (BM) and extracellular matrix in order to investigate whether any of them correlates with differentiation of prostatic adenocarcinoma (PAc). Two of these markers are collagen type IV (Col IV), the collagenous component of basement membrane, and fibronectin (Fn), an adhesion protein in extracellular matrix. Others are matrix metalloproteinase-9 (MMP-9), a type IV collagenase, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), which has a high affinity for MMP-9, and 67-kd laminin receptor (67LR), which belongs to the non-integrin laminin binding receptor family. STUDY DESIGN: Forty-three PAc cases with Gleason scores ranging between 5 and 10 and 10 benign prostatic hyperplasia (BPH) cases, the control group, were included in the study. Formalin-fixed and paraffin-embedded tissue slides from each case were immunostained with the avidin-biotin-peroxidase method. Immunoreactivity was determined by means of a scoring system similar to the Gleason scoring system. RESULTS: Overexpression of Col IV, Fn, 67LR and MMP-9 was detected in PAc as compared with BPH, whereas no difference was determined in TIMP-1 expression. Among these, only 67LR correlated statistically with Gleason score. CONCLUSION: Expression of 67LR in tumor cells was significantly increased in parallel to tumor grade. This may be useful in microscopic evaluation of PAc.

Renal cell carcinoma: new prognostic factors?

PURPOSE OF REVIEW: There are limited independent predictors of survival in patients with renal cell carcinoma. Factors related to the tumor, host and treatment may help us to predict prognosis to a certain extent. Prognostic indicators would enable selection of patients who can benefit from adjuvant therapy and thus should be enrolled in clinical trials. This review highlights developments in the identification of current prognosticators for patients with renal cell carcinoma. RECENT FINDINGS: Tumor stage, grade and patient-performance status are the known prognostic indicators in renal cell carcinoma. Besides these parameters, many molecular and cytogenetic markers were evaluated recently. Unfortunately, none of these parameters appear to be a better predictive prognostic factor than the usual staging and grading. Therefore, efforts to identify new markers for tumor proliferation and progression are still ongoing. It was recently reported that low carbonic anhydrase 9 staining may be an independent poor prognostic factor in patients with renal cell carcinoma. Moreover, there is increasing interest in prognostic indices and predictive algorithms for survival. Staging systems that combine the pathological features with additional prognostic variables have been constructed to predict outcome. The UCLA Integrated Staging System seems to be superior to staging alone in differentiating patients' survival. SUMMARY: Although the literature reviewed contains numerous promising clinical, histological, molecular and cytogenetic parameters, none of them has yet been shown to have an independent prognostic value