Long-term infection with urinary schistosomiasis has been associated with development of bladder cancer. However, bladder cancer is difficult to diagnose without invasive measures such as cystoscopy, thus there is little information on the epidemiological extent of the problem. Studies have been either case-control studies or case examinations in different geographical areas, estimating a schistosome-associated bladder cancer incidence of 3-4 cases per 100,000. We have used three indicators to examine the potential bladder cancer problem in an adult rural population in Ghana endemic for urinary schistosomiasis: (i) parasitological positivity; (ii) age prevalence of bladder damage from ultrasound scans; and (iii) detection of biomarkers associated with the presence of bladder cancer. Biomarkers were BLCA-4 test (urine) and nuclear morphometry or quantitative nuclear grading (QNG) of epithelial cells (urine sediment), which quantifies DNA ploidy status and nuclear morphometric descriptors, both of which can detect the presence of bladder cancer. Our data show an increasing association between age, severe bladder abnormalities and the occurrence of these biomarkers. Sixty-two of 73 cytopathology Papanicolaou-stained smears were seen to have squamous metaplasia. Although further investigations are needed, we suggest that schistosome-associated bladder cancer is an important public health concern in areas where Schistosoma haematobium is prevalent.

Background p300 impacts the transcription of several genes involved in key pathways critical to PCa progression. Therefore, we evaluated the prognostic value of p300 expression and its correlation with nuclear alterations seen in tumor cells in men with long term follow-up after radical prostatectomy (RP). Methods NCI Cooperative Prostate Cancer Tissue Resource tissue microarray cores of 92 RP cases (56 non-recurrences and 36 PSA recurrences) were utilized for the study. p300 expression was assessed by quantitative immunohistochemistry and nuclear alterations in Feulgen-stained nuclei were evaluated by digital image analysis using the AutoCyte™ Pathology Workstation. Cox proportional hazards regression, Spearman’s rank correlation, and Kaplan-Meier plots were employed to analyze the data. Results p300 expression significantly correlated with nuclear alterations seen in tumor cells; specifically with circular form factor (p=0.012) and minimum feret (p=0.048). p300 expression in high grade tumors (Gleason score ≥7) was significantly higher compared to low grade tumors (Gleason score <7) [17.7% vs. 13.7%, respectively, p=0.03]. TNM stage, Gleason score, and p300 expression were univariately significant in the prediction of PCa biochemical recurrence free survival (p≤0.05). p300 expression remained significant in the multivariate model (p=0.03) while Gleason score showed a trend toward significance (p=0.06). Patients with a Gleason score ≥7 and p300 expression >24% showed the highest risk for PCa biochemical recurrence (p=0.002). Conclusions p300 expression correlates with nuclear alterations seen in tumor cells and has prognostic value in predicting long-term PCa biochemical recurrence free survival.

Purpose: We assessed the association of quantitative clinical and pathologic information, including serum and tissue pro-prostate-specific antigen (proPSA) measurements, with outcomes among men with prostate cancer in an expectant management (active surveillance) program. Experimental Design: We identified 71 men enrolled in expectant management with frozen serum and tissue available from diagnosis: 39 subsequently developed unfavorable biopsies (Gleason score ≥7, ≥3 cores positive for cancer, >50% of any core involved with cancer), whereas 32 maintained favorable biopsies (median follow-up, 3.93 years). Serum total PSA, free PSA (fPSA), and [-2]proPSA were measured by the Beckman Coulter immunoassay. [-5/-7]proPSA was evaluated in cancer and benign-adjacent areas (BAA) by quantitative immunohistochemistry. Cox proportional hazards and Kaplan-Meier analyses were used to identify significant associations with unfavorable biopsy conversion. Results: The ratio [-2]proPSA/% fPSA in serum was significantly higher at diagnosis (0.87 ± 0.44 versus 0.65 ± 0.36 pg/mL; P = 0.02) in men developing unfavorable biopsies. [-5/-7]proPSA tissue staining was more intense (4104.09 ± 3033.50 versus 2418.06 ± 1606.04; P = 0.03) and comprised a greater fractional area (11.58 ± 7.08% versus 6.88 ± 5.20%; P = 0.01) in BAA of these men. Conclusions:In a prospective cohort of men enrolled into expectant management for prostate cancer, serum and tissue levels of proPSA at diagnosis are associated with need for subsequent treatment. The increase in serum proPSA/% fPSA might be driven by increased proPSA production from "premalignant" cells in the prostate BAA. (Clin Cancer Res 2009;15(23):7316-21) Prostate cancer is the second leading cause of cancer death among men in the United States, with an anticipated 186,320 newly diagnosed cases and 28,660 deaths in 2008 (1). Overdetection and overtreatment of cases unlikely to cause morbidity represent major dilemmas for prostate cancer management (2).In an effort to reduce the morbidity of overtreatment, expectant management, also known as active surveillance or watchful waiting, with delayed curative intervention has been proposed as a management strategy for low-grade, low-stage prostate cancer (3).