Prostatic carcinomas vary in their biological potential, even when stratified by grade and stage. Measurement of cellular proliferation by various methods has been shown to correlate with outcome for several human cancers, including prostatic carcinoma. Uptake of bromodeoxyuridine (BrdUrd), a thymidine analogue, has been accepted as a measure of cellular proliferative rate. However, the technique is somewhat complex, requiring incubation with fresh tissue. We compared cellular proliferation as measured by BrdUrd uptake with two more simple immunohistochemical methods in 44 prostatic adenocarcinoma specimens and correlated the results with standard clinical parameters. The tissue was obtained via needle biopsy, channel transurethral resection, and radical prostatectomy. Specimens were incubated in vitro with BrdUrd and then fixed and paraffin embedded. Sections were immunohistochemically stained with antibodies to BrdUrd, proliferating cell nuclear antigen (PCNA), and Ki-67. At least 1,000 cells were scored, and a labeling index (LI) was calculated (number of positive cells/total number of cells). The mean LI determined by all three indices was low (BrdUrd = 3.0, PCNA = 7.0, Ki-67 = 3.4), consistent with the knowledge that prostatic tumors grow slowly. In 36 patients who had not been treated at the time of analysis, the LI as determined by all three methods correlated well with clinical stage and pathological grade. Furthermore, the LIs discriminated between those with tumor confined to the prostate and those with extension to the seminal vesicles, lymph nodes, or bone (P = 0.003, 0.004, 0.008 for BrdUrd, PCNA, and Ki-67, respectively). The LIs for PCNA and Ki-67 correlated well with that for BrdUrd (r = 0.84; r = 0.85), while the LIs for Ki-67 and PCNA correlated slightly less well with each other (r = 0.78). PCNA and Ki-67 expression appear to reflect essentially the same biological process as BrdUrd uptake. Either can substitute for BrdUrd as a measure of cellular proliferation, and Ki-67 seems to offer the fewest technical problems.

Health-Related Quality of Life (HRQOL) is an important outcome measure in the study of prostate cancer. There are few data regarding the effect of sociodemographic variables, such as insurance status, educational level, marital status or income, on HRQOL. We examined whether these or other sociodemographic and clinical variables are predictive of HRQOL outcomes using an observational database of prostate cancer patients accrued from a wide array of clinical practice settings.We studied 131 patients with newly-diagnosed prostate cancer who had been followed for at least nine months. Patients were enrolled in CaPSURE TM , a large, observational database of patients with prostate cancer. General and diseasespeci®c HRQOL were measured with established, validated instruments at diagnosis and nine months later. Sociodemographic data and co-morbidity counts were recorded at baseline. Multivariate regression analysis was used to determine whether sociodemographic or clinical variables were predictive of baseline HRQOL or HRQOL changes during the study period.Several sociodemographic and clinical variables demonstrated signi®cant associations with HRQOL. We found improvements in general and diseasespeci®c domains of HRQOL during the nine months after diagnosis. For married patients, Emotional Well-Being and Family Functioning scores were better at baseline ( 11.8, P`0.02), but Family Functioning declined over the nine month study period (À18.5, P 0.0006). Older patients had slightly better baseline performance in several domains of HRQOL, but experienced greater HRQOL decrements over time than did younger patients. Increasing comorbidity was associated with worse baseline general HRQOL. Early tumor stage was predictive of better scores in general HRQOL domains at baseline. Limited palpable disease stage (T2A/T2B) was predictive of worse Sexual Function and Sexual Bother at nine months (À8.6, P 0.04; À24, P 0.008).After initial decreases, patients appear to experience an improvement in general and disease-speci®c HRQOL within nine months of initial diagnosis with prostate cancer. Marital status is associated with better HRQOL, while advancing age is associated with more signi®cant HRQOL declines over time. Patients with lower stage disease were noted to have better general HRQOL at baseline, although decreases in the physical domains were noted at nine months. These data shed new light on patients' experience with prostate cancer and suggest that HRQOL outcomes over time may occur in a predictable manner.

Prostate cancer is the second most common malignancy in men worldwide and consists of a mixture of tumor and non-tumor cell types. To characterize the prostate cancer tumor microenvironment, we performed single-cell RNA-sequencing on prostate biopsies, prostatectomy specimens, and patient-derived organoids from localized prostate cancer patients. We identify a population of tumor-associated club cells that may act as progenitor cells and uncover heterogeneous cellular states in prostate epithelial cells marked by high androgen signaling states that are enriched in prostate cancer. ERG- tumor cells, compared to ERG+ cells, demonstrate shared heterogeneity with surrounding luminal epithelial cells and appear to give rise to common tumor microenvironment responses. Finally, we show that prostate epithelial organoids recapitulate tumor-associated epithelial cell states and are enriched with distinct cell types and states from their parent tissues. Our results provide diagnostically relevant insights and advance our understanding of the cellular states associated with prostate carcinogenesis.

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