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Purpose: To conduct a population-based study to determine whether the use of GnRH agonist and antiandrogens are associated with an increased risk of cardio-cerebrovascular disease (CCVD) in Asian patients with prostate cancer using the National Health Insurance Service-Elderly Cohort Database (NHIS-ECD). Materials and Methods: We included a total of 2,413 men aged 60 years or older with prostate cancer between January 2003 and December 2008. Outcomes of interest included the first occurrence of cardiovascular events [acute myocardial infarction (AMI), ischemic heart disease (IHD)] and cerebrovascular events [ischemic stroke (IS), and cerebrovascular disease (CVD)]. Results: The 5-year AMI-free rates of patients diagnosed with prostate cancer and treated with GnRH agonists, antiandrogens alone, or androgen deprivation therapy (ADT)-naïve interventions were 97.0%, 96.5%, and 98.3%, respectively, while the 5-year IHD-free rates were 93.2%, 92.3%, and 94.5%, respectively. Exposure to GnRH agonists or antiandrogen regimens did not significantly increase the risk of AMI or IHD compared to ADT-naïve treatment in multivariate Cox proportional-hazards models after adjusting for other covariates. Five-year IS-free rates of patients exposed to GnRH agonists, antiandrogens alone, and those with ADT-naïve prostate cancer were 94.8%, 94.7%, and 95.5%, respectively, while the five-year CVD-free rates were 92.9%, 93.3%, and 94.6%, respectively. Cox proportional-hazards models also failed to show that men who received GnRH agonist or antiandrogen treatment alone carried a significantly increased risk for IS or CVD compared to ADT-naïve patients. Conclusions: The current study based on Asian population suggests that treatment with neither GnRH agonist nor antiandrogens increases the risk of cardio-cerebrovascular disease compared to patients with ADT-naïve prostate cancer.
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Objective: To explore whether cultured CTC from bladder-cancer patients originate from bladder cancer and share chromosomal abnormalities, by means of a fluorescence in situ hybridization (FISH) test. Methods: A total of 15 ml of blood was collected from the patients with bladder cancer before treatment began. Isolated CTCs were divided into 5 ml for CTC enumeration and 10 ml for CTC culture. CTCs were counted by immunofluorescent staining with vimentin, cytokeratin, CD45, and DAPI antibody. CTCs were cultured using isolated CTCs in 96-well plates of Mesenchymal Stem Cell Growth Medium for 16~18 days. The resulting cultured CTCs from 20 men with bladder cancer were analyzed by Urovysion FISH. Results: Common gains were on chromosome 3, 7, and 17 in 20 (74.1%), 14 (51.9%), and 20 (74.1%) of 27 patients, respectively. Polysomy was detected on chromosomes 3 and 7 in 9 patients (33.3%). Polysomy involving two chromosomes was observed in 16 (59.3%, chromosome 3 and 17) and 9 patients (33.3%, chromosome 7 and 17) in the same cell. Among the patients with isolated gain, 17 (63.0%) met the positive criteria for Urovysion FISH. Homozygous deletion of 9p21, 5 (18.5%) involved more than 12 cells. Among the different patient cohorts, positive results based on the Urovysion criteria were obtained in cultured CTCs derived from 19 (70.4%) patients. Conclusion: Application of FISH Urovysion to cultured CTCs from bladder cancer could be an effective first step to confirm their origin and sharing of chromosomal abnormalities.
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Purpose: We aimed to investigate the expression of FOXM1 and to determine the relationships between FOXM1 expression and clinicopathologic characteristics in patients with PCa. Furthermore, we reconfirmed the prognostic impact of FOXM1 in different cohorts using already published data. Patients and Methods: Formalin-fixed, paraffin-embedded tissues were collected from patients with low- (n=17), intermediate- (n=36), and high-risk (n=29) disease, from patients with CRPC (n=2) and from patients with BPH (n=28). To analyze FOXM1 expression, we performed IHC analyses. Also, we analyzed gene expression data from cBioPortal to evaluate the associations between FOXM1 alteration and prognosis of PCa. Results: FOXM1 expression measured using Allred score differed between patients with BPH, and low-, intermediate-, and high-risk PCa (0.3, 1.5, 4.8, and 6.2, respectively; p<0.001). Patients with high FOXM1 expression had higher preoperative PSA levels (p=0.023), more advanced tumor stages (p=0.047), and higher pathologic Gleason score (p<0.001) than those with low FOXM1 expression. ROC curve analysis indicated that FOXM1 expression was a useful marker for discriminating PCa from BPH (AUC 0.851, 95% CI 0.783-0.920) and for discriminating high-risk PCa from low- and intermediate-risk PCa (AUC 0.807, 95% CI 0.719-0.894). In multivariate analyses, high FOXM1 expression was an independent predictor of BCR. Finally, in the TCGA dataset, FOXM1 alteration was associated with poor overall (p=4.521e-4) and disease-free survival (p=0.0108). Conclusions: In patients with PCa, high FOXM1 expression was associated with advanced tumor stages, high Gleason score, and poor prognosis. These data suggest a role of FOXM1 in biologically and clinically aggressive PCa.
