Sengupta, Shomik

Objective To analyse the trends in opportunistic PSA screening in A ustralia, focusing on younger men (<55 years of age), to examine the effects of this screening on transrectal ultrasonography ( TRUS )‐guided biopsy rates and to determine the nature of prostate cancers ( PC as) being detected. Subjects and Methods All men who received an opportunistic screening PSA test and TRUS ‐guided biopsy between 2001 and 2008 in A ustralia were analysed using data from the A ustralian C ancer registry ( A ustralian I nstitute of H ealth and W elfare) and Medicare databases. The V ictorian cancer registry was used to obtain G leason scores. Age‐standardized and age‐specific rates were calculated, along with the incidence of PC a, and correlated with G leason scores. Results A total 5 174 031 PSA tests detected 128 167 PC as in the period 2001–2008. During this period, PSA testing increased by 146% (a mean of 4629 tests per 100 000 men annually), with 80 and 59% increases in the rates of TRUS ‐guided biopsy and incidence of PC a, respectively. The highest increases in PSA screening occurred in men <55 years old and up to 1101 men had to be screened to detect one incident case of PC a (0.01%). Screening resulted in two thirds of men aged <55 years receiving a negative TRUS biopsy. There was no correlation with G leason >7 tumours in patients aged <55 years. Conclusion Despite the ongoing controversy about the merits of PCa screening, there was an increase in PSA testing, especially in men <55 years old, leading to a modestly higher incidence of PC a in A ustralia. Overall, PSA screening was associated with high rates of negative TRUS ‐biopsy and the detection of low/intermediate grade PCa among younger patients.

AbstractPurpose: Regulatory T cells (Tregs) have been implicated as inhibitors of antitumoral immunity, and evidence suggests that elimination of Tregs may augment natural and pharmacologic immunity. We tested for the presence of putative Tregs within renal cell carcinoma (RCC) tumors.Experimental Design: We identified 170 patients who underwent radical or partial nephrectomy for clear cell RCC between 2000 and 2002. Specimens were stained with anti-CD4, anti-CD25, and anti-Foxp3 antibodies and examined using confocal microscopy. Associations of CD4+CD25+Foxp3− and CD4+CD25+Foxp3+ T cells with death from RCC were evaluated using Cox proportional hazards regression models.Results: At last follow-up, 46 of 170 patients had died; of these, 37 died from RCC at a median of 1.4 years following nephrectomy (range, 0-4.4). Among the 124 remaining patients, median follow-up was 3.7 years (range, 0-5.7). Forty-three (25.3%) tumors harbored CD4+CD25+Foxp3+ T cells. The presence of Foxp3+ T cells was not significantly associated with RCC death univariately. One hundred forty-three (84.1%) tumors harbored CD4+CD25+Foxp3− T cells. The indicator for ≥10% CD4+CD25+Foxp3− T cells was significantly associated with RCC death univariately [risk ratio (RR), 2.60; 95% confidence interval (95% CI), 1.35-4.98; P = 0.004], after adjusting for tumor B7-H1 expression (RR, 2.53; 95% CI, 1.32-4.85; P = 0.005) and lymphocytic infiltration (RR, 2.53; 95% CI, 1.32-4.87; P = 0.005).Conclusions: Increased presence of CD4+CD25+Foxp3+ T cells was not significantly associated with RCC death. In contrast, CD4+CD25+Foxp3− T cells, which may represent a unique set of Tregs or activated helper T cells, was significantly associated with outcome.

Abstract B7-H1 participates in T-cell costimulation functioning as a negative regulator of immunity. Recent observations suggest that B7-H1 is expressed by renal cell carcinoma (RCC) tumor cells and is associated with poor prognosis. However, outcome analyses have been restricted to patients with fresh-frozen tissue and limited follow-up. We report the clinical effect of B7-H1 in RCC patients with a median of 10 years of follow-up. Between 1990 and 1994, 306 patients underwent nephrectomy for clear cell RCC and had paraffin tissue available for review. We did immunohistochemistry with anti-B7-H1 and conducted outcome analyses. Among the 306 patients, 73 (23.9%) harbored tumors with B7-H1 expression. Patients with tumor B7-H1 were at a significantly increased risk of both death from RCC [risk ratio (RR), 3.92; P &lt; 0.001] and overall mortality (RR, 2.37; P &lt; 0.001). The 5-year cancer-specific survival rates were 41.9% and 82.9% for patients with and without tumor B7-H1, respectively. In a multivariate model, tumor B7-H1 remained associated with cancer-specific death even after adjusting for tumor-node-metastasis stage, grade, and performance status (RR, 2.00; P = 0.003). In the subset of 268 patients with localized RCC, tumor B7-H1 was significantly associated with metastatic cancer progression (RR, 3.46; P &lt; 0.001) and death from RCC (RR, 4.13; P &lt; 0.001) even after adjusting for stage, grade, and performance status (RR, 1.78, P = 0.036). RCC patients with tumor B7-H1 are at significant risk of rapid cancer progression and accelerated rates of mortality. B7-H1 may function as a key determinant in RCC, abrogating immune responses directed against this immunogenic tumor. (Cancer Res 2006; 66(7): 3381-5)