Mast cells affect growth in various humanCancer growth is dependent on the reciprocal interaction between tumor cells and their microenvironment. Cancerassociated fibroblasts, 1 vascular cells, and inflammatory cells such as macrophages [2][3][4] have been shown to promote prostate tumor growth. Mast cells are also of importance for tumor growth and have been shown to affect angiogenesis 5-7 but are also potent regulators of inflammation and thus their specific function during tumor progression is complex and shows significant plasticity. 8 -10 Their role in prostate cancer (PC) in patients was recently explored in two separate studies using tryptase and c-Kit as markers for mast cells. These studies lacked the discrepancy between intra-and peritumoral mast cells and did not identify mast cells as independent prognostic variables. One of the studies showed that tryptase-positive mast cells were related to poor outcome in PC patients. 12 The other study analyzed c-Kit-positive cells in tumor samples from PC patients and found an association between increased mast cell numbers and a favorable prognosis. 13Castration therapy is the gold standard for treatment of patients with metastatic PC, but in the majority of cases the formation of castrate-resistant prostate tumors is inevitable. The mechanisms behind the relapse are not fully understood but could be related to changes in the androgen receptor and the tumor stroma.

Objective To investigate the prognostic value of the Gleason score in prostate cancer. Patients and methods A consecutive series of 305 men with prostate cancer diagnosed at transurethral resection (1975)(1976)(1977)(1978)(1979)(1980)(1981)(1982)(1983)(1984)(1985)(1986)(1987)(1988)(1989)(1990) and with no curative treatment was analysed. There was no assessment of prostate-specific antigen level during this period. The mean (range) age at diagnosis was 73.7 (52-95) years and the mean follow-up was 6.4 (0-22) years. The influence of Gleason score and the percentage of the specimen area with tumour (% cancer) on diseasespecific survival were assessed using Kaplan-Meier analyses. Results Of 305 cancers, 22% had a Gleason score of 4-5, 29% of 6, 18% of 7 and 32% of 8-10. At the follow-up, 89% of the men had died, of whom 42% had died from prostate cancer. The disease-specific 10-year survival was 56%. The disease-specific mean survival (DSMS) for Gleason score 4-5, 6, 7 and 8-10 was 20, 16, 10 and 5 years, respectively (P<0.001).The DSMS did not differ significantly between Gleason 4 and 5 or between 8-10. There was a trend towards shorter survival for Gleason 4+3=7 (DSMS 9 years) than GS 3+4=7 (DSMS 13 years; P=0.16). Gleason score and % cancer were independent predictors of DSMS (P<0.001). Conclusion The long-term prognosis of prostate cancer on deferred treatment is predicted well by the Gleason score. Four prognostic categories of prostate cancer are suggested, i.e. Gleason score 4-5, 6, 7 and 8-10.

No abstract

The TMPRSS2-ERG gene fusion is found in approximately half of all prostate cancers. The functional and prognostic significance of TMPRSS2-ERG is, however, not fully understood. Based on a historical watchful waiting cohort, an association between TMPRSS2-ERG, evaluated as positive immune staining, and shorter survival of prostate cancer patients was identified. Expression of ERG was also associated with clinical markers such as advanced tumor stage, high Gleason score, presence of metastasis and prognostic tumor cell markers such as high Ki67, pEGFR and pAkt. Novel associations between TMPRSS2-ERG and alterations in the tumor stroma, for example, increased vascular density, hyaluronan and PDGFRβ and decreased Caveolin-1, all known to be associated with an aggressive disease, were found. The present study suggests that the TMPRSS2-ERG fusion gene is associated with a more aggressive prostate cancer phenotype, supported by changes in the tumor stroma.

Background A disadvantage of prostate-specific antigen (PSA) for the early detection of prostate cancer (PCa) is that many men must be screened, biopsied, and diagnosed to prevent one death. Objective To increase the specificity of screening for lethal PCa at an early stage. Design, setting, and participants We conducted a case–control study nested within a population-based cohort. PSA and three additional kallikreins were measured in cryopreserved blood from a population-based cohort in Västerbotten, Sweden. Of 40 379 men providing blood at ages 40, 50, and 60 yr from 1986 to 2009, 12 561 men were followed for >15 yr. From this cohort, the Swedish Cancer Registry identified 1423 incident PCa cases, 235 with distant metastasis. Outcome measurements and statistical analysis Risk of distant metastasis for different PSA levels and a prespecified statistical model based on the four kallikrein markers. Results and limitations Most metastatic cases occurred in men with PSA in the top quartile at age 50 yr (69%) or 60 yr (74%), whereas 20-yr risk of metastasis for men with PSA below median was low (≤0.6%). Among men with PSA >2 ng/ml, a prespecified model based on four kallikrein markers significantly enhanced the prediction of metastasis compared with PSA alone. About half of all men with PSA >2 ng/ml were defined as low risk by this model and had a ≤1% 15-yr risk of metastasis. Conclusions Screening at ages 50–60 yr should focus on men with PSA in the top quartile. A marker panel can aid biopsy decision making. Patient summary For men in their fifties, screening should focus on those in the top 10% of PSA scores because close to half of subsequent cases of distant metastasis are found in this group. Testing of four kallikrein markers in men with an elevated PSA could aid biopsy decision making.