Serum testosterone as a biomarker for second prostatic biopsy in men with negative first biopsy for prostatic cancer and PSA>4ng/mL, or with PIN biopsy result

Abstract Introduction: Data from animal, clinical and prevention studies support the role of androgens in prostate cancer growth, proliferation and progression. Results of serum based epidemiologic studies in humans, however, have been inconclusive. The present study aims to define whether serum testosterone can be used as a predictor of a positive second biopsy in males considered for re-biopsy. Material and Methods: The study included 320 men who underwent a prostatic biopsy in our department from October 2011 until June 2012. Total testosterone, free testosterone, bioavailable testosterone and prostate pathology were evaluated in all cases. Patients undergoing a second biopsy were identified and biopsy results were statistically analyzed. Results: Forty men (12.5%) were assessed with a second biopsy. The diagnosis of the second biopsy was High Grade Intraepithelial Neoplasia in 14 patients (35%) and Prostate Cancer in 12 patients (30%). The comparison of prostatic volume, total testosterone, sex hormone binding globulin, free testosterone, bioavailable testosterone and albumin showed that patients with cancer of the prostate had significantly greater levels of free testosterone (p=0.043) and bioavailable T (p=0.049). Conclusion: In our study, higher free testosterone and bioavailable testosterone levels were associated with a cancer diagnosis at re-biopsy. Our results indicate a possible role for free and bioavailable testosterone in predicting the presence of prostate cancer in patients considered for re-biopsy.

Serum testosterone as a biomarker for second prostatic biopsy in men with negative first biopsy for prostatic cancer and PSA>4ng/mL, or with PIN biopsy result.

INTRODUCTION: Data from animal, clinical and prevention studies support the role of androgens in prostate cancer growth, proliferation and progression. Results of serum based epidemiologic studies in humans, however, have been inconclusive. The present study aims to define whether serum testosterone can be used as a predictor of a posi¬tive second biopsy in males considered for re-biopsy. MATERIAL AND METHODS: The study included 320 men who underwent a prostatic biopsy in our department from October 2011 until June 2012. Total testosterone, free testos¬terone, bioavailable testosterone and prostate pathology were evaluated in all cases. Patients undergoing a second biopsy were identified and biopsy results were statistically analyzed. RESULTS: Forty men (12.5%) were assessed with a second biopsy. The diagnosis of the second biopsy was High Grade Intraepithelial Neoplasia in 14 patients (35%) and Prostate Cancer in 12 patients (30%). The comparison of prostatic volume, total testosterone, sex hormone binding globulin, free testosterone, bioavailable testosterone and albumin showed that patients with cancer of the prostate had significantly greater levels of free testosterone (p=0.043) and bioavailable T (p=0.049). CONCLUSION: In our study, higher free testosterone and bioavailable testosterone levels were associated with a cancer diagnosis at re-biopsy. Our results indicate a possible role for free and bioavailable testosterone in predicting the presence of prostate cancer in patients considered for re-biopsy.

Serum levels of hypothalamic-pituitary-testicular axis hormones in men with or without prostate cancer or atypical small acinar proliferation.

INTRODUCTION: Substantial controversy exists regarding the association between testosterone serum levels and prostate cancer. OBJECTIVE: To evaluate the levels of hypothalamic-pituitary-testicular axis hormones in the sera of men with prostate cancer and atypical small acinar proliferation as well as those with normal biopsies. METHODS: A study cohort of 186 men with suspected prostate cancer who had undergone transrectal prostate biopsies was used in this study. The patients were divided into the following three groups based on the histology of the biopsy samples: no neoplasia, atypical small acinar proliferation or prostate cancer. Demographic data were also collected. Levels of total testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, and serum prostate-specific antigen were measured in blood samples. RESULTS: Initially, 123 men were found to be without neoplasia, 26 with atypical small acinar proliferation and 37 with prostate cancer. After a second biopsy was taken from the men diagnosed with atypical small acinar proliferation, the diagnoses were revised: 18 were diagnosed with atypical small acinar proliferation and 45 with prostate cancer. No significant differences between the groups were identified regarding age, smoking history, chronic diseases, body mass index or PSA levels (P >.0.05). The mean serum levels of testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin and estradiol were similar in all of the groups (P >.0.05). Furthermore, in individuals with prostate cancer, the Gleason scores and prevalence of hypogonadism were not significantly different (P.> 0.05). CONCLUSION: The present study revealed no difference in the serum levels of testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin or estradiol in men without neoplasia compared with those with atypical small acinar proliferation or prostate cancer.

Serum levels of hypothalamic-pituitary-testicular axis hormones in men with or without prostate cancer or atypical small acinar proliferation

INTRODUCTION: Substantial controversy exists regarding the association between testosterone serum levels and prostate cancer. OBJECTIVE: To evaluate the levels of hypothalamic-pituitary-testicular axis hormones in the sera of men with prostate cancer and atypical small acinar proliferation as well as those with normal biopsies. METHODS: A study cohort of 186 men with suspected prostate cancer who had undergone transrectal prostate biopsies was used in this study. The patients were divided into the following three groups based on the histology of the biopsy samples: no neoplasia, atypical small acinar proliferation or prostate cancer. Demographic data were also collected. Levels of total testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, and serum prostate-specific antigen were measured in blood samples. RESULTS: Initially, 123 men were found to be without neoplasia, 26 with atypical small acinar proliferation and 37 with prostate cancer. After a second biopsy was taken from the men diagnosed with atypical small acinar proliferation, the diagnoses were revised: 18 were diagnosed with atypical small acinar proliferation and 45 with prostate cancer. No significant differences between the groups were identified regarding age, smoking history, chronic diseases, body mass index or PSA levels (P >.0.05). The mean serum levels of testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin and estradiol were similar in all of the groups (P >.0.05). Furthermore, in individuals with prostate cancer, the Gleason scores and prevalence of hypogonadism were not significantly different (P.> 0.05). CONCLUSION: The present study revealed no difference in the serum levels of testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin or estradiol in men without neoplasia compared with those with atypical small acinar proliferation or prostate cancer.

Vascular endothelial growth factor (VEGF) and prostate pathology.

PURPOSE: Previous studies suggest that vascular endothelial growth factor (VEGF) circulating levels might improve identification of patients with prostate cancer but results are conflicting. Our aim was to compare serum VEGF levels across different prostate pathologies (including benign prostatic hyperplasia, prostatitis, high grade prostate intraepithelial neoplasia and prostate cancer) in patients at high risk of prostate cancer. MATERIALS AND METHODS: We consecutively enrolled 186 subjects with abnormal digital rectal examination and/or total PSA (tPSA) > or = 2.5 ng/mL. Blood was collected before diagnostic ultrasound guided trans-rectal prostate biopsy, or any prostate oncology treatment, to measure PSA isoforms and VEGF. Unconditional logistic regression was used to compute age-, tPSA- and free/total PSA-adjusted odds ratios (OR) and respective 95% confidence intervals (95% CI) for the association between serum VEGF and different prostatic pathologies. RESULTS: Prostate biopsy main diagnoses were normal or benign prostatic hyperplasia (27.3%), prostatitis (16.6%), and prostatic cancer (55.0%). The median VEGF levels (ng/mL) in these groups were 178.2, 261.3 and 266.4 (p = 0.029), respectively, but no significant differences were observed for benign vs. malignant pathologies (215.2 vs. 266.4, p = 0.551). No independent association was observed between VEGF (3rd vs. 1st third) and prostate cancer, when compared to benign conditions (adjusted OR = 1.44; CI 95%: 0.64-3.26). CONCLUSIONS: In patients at high risk of prostate cancer, circulating VEGF levels have no clinical role in deciding which patients should be submitted to prostate biopsy. Prostatitis patients, often with higher PSA levels, also present high serum levels of VEGF, and their inclusion in control groups might explain the heterogeneous results in previous studies.

Vascular endothelial growth factor (VEGF) and prostate pathology

PURPOSE: Previous studies suggest that vascular endothelial growth factor (VEGF) circulating levels might improve identification of patients with prostate cancer but results are conflicting. Our aim was to compare serum VEGF levels across different prostate pathologies (including benign prostatic hyperplasia, prostatitis, high grade prostate intraepithelial neoplasia and prostate cancer) in patients at high risk of prostate cancer. MATERIALS AND METHODS: We consecutively enrolled 186 subjects with abnormal digital rectal examination and/or total PSA (tPSA) = 2.5 ng/mL. Blood was collected before diagnostic ultrasound guided trans-rectal prostate biopsy, or any prostate oncology treatment, to measure PSA isoforms and VEGF. Unconditional logistic regression was used to compute age-, tPSA- and free/total PSA-adjusted odds ratios (OR) and respective 95 percent confidence intervals (95 percent CI) for the association between serum VEGF and different prostatic pathologies. RESULTS: Prostate biopsy main diagnoses were normal or benign prostatic hyperplasia (27.3 percent), prostatitis (16.6 percent), and prostatic cancer (55.0 percent). The median VEGF levels (ng/mL) in these groups were 178.2, 261.3 and 266.4 (p = 0.029), respectively, but no significant differences were observed for benign vs. malignant pathologies (215.2 vs. 266.4, p = 0.551). No independent association was observed between VEGF (3rd vs. 1st third) and prostate cancer, when compared to benign conditions (adjusted OR = 1.44; CI 95 percent: 0.64-3.26). CONCLUSIONS: In patients at high risk of prostate cancer, circulating VEGF levels have no clinical role in deciding which patients should be submitted to prostate biopsy. Prostatitis patients, often with higher PSA levels, also present high serum levels of VEGF, and their inclusion in control groups might explain the heterogeneous results in previous studies.

Malignant lesions in the ventral prostate of alloxan-induced diabetic rats.

The aim of this study was to evaluate the changes caused by chronic diabetes in the rat ventral prostate and to establish a correlation between diabetes and the development of prostatic lesions. Male rats received alloxan (42 mg/kg b.w.) to induce diabetes. Ninety days after diabetes diagnosis, animals were sacrificed and the ventral prostate was removed and prepared for general and immunohistochemical analyses. The total area showing different types of lesions was estimated. Diabetes led to a decrease in the body and prostatic weights, as well as in testosterone levels. The prostate morphology and stereology showed high variation in the diabetic group. Some animals had light changes; the great majority had an intense epithelial atrophy; and other rats showed premalignant and malignant lesions in the prostate. Such epithelial atrophy was, in some samples, combined with chronic inflammation, similar to proliferative inflammatory atrophy (PIA). The diabetic group also presented high incidence of prostatitis, adenocarcinoma and prostatic intra-epithelial neoplasia (PIN). Samples with adenocarcinoma had poorly differentiated acini with high levels of cellular proliferation and nuclear atypia. These lesions exhibited an invasive feature showing Bcl-2-positive cells and interruptions in the basement membrane. An association of PIA, PIN and adenocarcinoma was detected in one sample. Reduced androgen levels have a synergic effect to insulin dysfunction promoting negative effects in the rat prostate. Diabetic individuals had a high incidence of prostatitis, and this inflammation could stimulate the incidence of other forms of prostatic pathology.

A randomized trial of lycopene supplementation in Tobago men with high prostate cancer risk.

This unblinded, randomized, Phase I clinical trial was conducted to determine whether lycopene supplementation lowered serum prostate specific antigen (PSA), surrogate endpoint for prostate cancer initiation or progression, in men with elevated prostate cancer risk. Afro-Caribbean men (n=81) with high-grade prostatic intraepithelial neoplasia, atypical foci or repeated non-cancerous biopsies, ascertained in a population-based screening program, were randomized to four months intervention with 30 mg/day lycopene (Lyc-O-Mato) plus a multivitamin, or to multivitamin, only. Serum PSA and lycopene were compared at randomization, 1, and 4 mo using two-sided chi2 and t-tests for independent samples. Treatment groups were similar at baseline. Serum lycopene levels approximately doubled in the lycopene intervention group. Serum PSA declined during the first month of treatment, but returned to randomization level by month 4. The PSA response was nearly identical in both treatment groups. No adverse effects attributed to lycopene supplementation were documented. We conclude that the PSA lowering response to antioxidant supplementation observed in previous 3-wk studies in men awaiting prostatectomy may have been a transient response, perhaps not specific to lycopene. Lowering of serum PSA may not be an appropriate endpoint for the long-term studies needed to evaluate lycopene supplementation for reducing prostate cancer initiation or progression.

The endothelial nitric oxide synthase Glu-298-Asp polymorphism and its mRNA expression in the peripheral blood of patients with prostate cancer and benign prostatic hyperplasia.

BACKGROUND: The endothelial nitric oxide synthase (ecNOS) has an important role in vascular development and in the carcinogenesis process of prostate cancer (PCa). The nitric oxide (NO) production may promote cancer progression by providing a selective growth advantage to tumor cells, by angiogenic stimulus and by direct DNA damage. METHODS: The present study aimed at evaluating the ecNOS Glu-298-Asp polymorphism by the PCR-RFLP technique, associating genotypes with gene expression levels and the tumor biomarker, Prostate Cancer Antigen (DD3), through semi-quantitative RT-PCR. Pre-surgical peripheral blood samples from 160 patients were analyzed: 84 PCa, 11 prostate intraepithelial neoplasia (PIN) and 65 benign prostatic hyperplasia (BPH). RESULTS: The GG and GT Glu-298-Asp genotypes were associated with positive DD3 expression in the peripheral blood, presenting a 3.32-fold higher risk of PCa occurrence. There was no association between genotypes and ecNOS mRNA expression levels; however, the presence of the G allele is closely related to the hematogenous dissemination event of tumoral cells, as evidenced by the DD3 positivity. The higher G allele frequency among pT3 and pT4 staged PCa patients suggests that this would be associated with advanced phenotypes of the disease and may also be contributing to higher NO levels, causing cancer progression. CONCLUSIONS: The G allele may have a secondary influence on the prostate cancer predisposition, but an essential role on the event of tumor cells hematogenous dissemination, probably due to the angiogenic stimulus.

Clinicopathological features of prostate cancer in Jamaican men.

OBJECTIVE: To document the clinicopathological features of prostate cancer in a cohort of Jamaican men, and to determine which of these features are of prognostic significance in this population. PATIENTS AND METHODS: The clinical and pathological findings in 99 patients with prostate cancer (diagnosed consecutively after biopsy, in the Department of Pathology at the University of the West Indies) between 1993 and 1997 were reviewed retrospectively. Biopsy specimens included 74 needle biopsies and 25 transurethral resection (TUR) specimens. RESULTS: The mean age at diagnosis was 72.3 years and 79 patients (80%) were symptomatic. The median (range, interquartile range) serum prostate-specific antigen (PSA) value at diagnosis was 37 (1-2100, 2-750) ng/mL; 63% of the patients had clinical stage T1 or T2 disease. Most (60%) of the cancers had a Gleason score of 8-10. Perineural invasion was present in a third of cases overall; high-grade prostatic intraepithelial neoplasia and periprostatic involvement were present in 18% and 8% of biopsies, respectively. The median percentage involvement of all biopsy samples was 37%, that for needle biopsies 47% and for TUR specimens 14%. Of the 90 patients with complete follow-up data, 37 (41%) died; the cause was progressive disease in 19 (51%). The mean (sd, range) survival was 41.3 (19.7, 1-73) months. On univariate analysis, age, PSA level, tumour stage, Gleason score, perineural involvement and periprostatic involvement were significantly associated with an increased risk of dying from prostatic cancer; in a multivariate model, PSA and tumour stage (4 vs. 1) were the only independent factors. CONCLUSIONS: The mean PSA values at the time of diagnosis, the median percentage of biopsy involvement by cancer and the number of patients with tumours of high histological grade were comparatively high, probably reflecting the patients' relatively late clinical presentation. Established prognostic markers were predictive of the risk of death from prostate cancer.